ClinVar Genomic variation as it relates to human health
NM_001083116.3(PRF1):c.272C>T (p.Ala91Val)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic(1); Uncertain significance(2); Benign(3); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001083116.3(PRF1):c.272C>T (p.Ala91Val)
Variation ID: 13718 Accession: VCV000013718.33
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q22.1 10: 70600631 (GRCh38) [ NCBI UCSC ] 10: 72360387 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 11, 2015 Apr 6, 2024 Mar 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001083116.3:c.272C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001076585.1:p.Ala91Val missense NM_005041.5:c.272C>T NM_005041.6:c.272C>T NP_005032.2:p.Ala91Val missense NC_000010.11:g.70600631G>A NC_000010.10:g.72360387G>A NG_009615.1:g.7145C>T LRG_94:g.7145C>T LRG_94t1:c.272C>T P14222:p.Ala91Val - Protein change
- A91V
- Other names
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- Canonical SPDI
- NC_000010.11:70600630:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.01318 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.01318
1000 Genomes Project 30x 0.01327
The Genome Aggregation Database (gnomAD) 0.02791
Trans-Omics for Precision Medicine (TOPMed) 0.02914
The Genome Aggregation Database (gnomAD), exomes 0.02932
Exome Aggregation Consortium (ExAC) 0.03106
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PRF1 | - | - |
GRCh38 GRCh37 |
662 | 679 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (1) |
no assertion criteria provided
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Aug 15, 2007 | RCV000014719.7 | |
Pathogenic; risk factor (3) |
criteria provided, multiple submitters, no conflicts
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Mar 18, 2021 | RCV000224458.7 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Jul 13, 2022 | RCV000456018.9 | |
Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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Mar 25, 2024 | RCV000547554.19 | |
Benign (1) |
criteria provided, single submitter
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Jan 29, 2022 | RCV002260967.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 30, 2024 | RCV003398509.5 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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risk factor
(Mar 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000617803.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
Comment:
Identified in individuals with familial hemophagocytic lymphohistiocytosis and acute lymophoblastic leukemia; however, the A91V variant has also been identified in both unaffected relatives and unaffected … (more)
Identified in individuals with familial hemophagocytic lymphohistiocytosis and acute lymophoblastic leukemia; however, the A91V variant has also been identified in both unaffected relatives and unaffected controls (Zur Stadt et al., 2004; Santoro et al., 2005; An et al., 2013); Functional studies suggest that the A91V variant results in decreased levels of perforin expression, with partial loss of protein function and stability (Voskoboinik et al., 2005; House et al., 2015); This variant is associated with the following publications: (PMID: 33256384, 32150605, 32198610, 32342501, 32542393, 32300447, 31932842, 30957677, 29263817, 30343897, 30287596, 14757862, 24916509, 27622035, 28863861, 27153395, 27872624, 15342365, 23592409, 26597256, 24632576, 22970278, 25937001, 25121636, 24309606, 22437823, 16611257, 25776844, 23073290, 25354579, 18496551, 17311987, 17475905, 15741215, 12229880, 21881043, 15755897, 15921391) (less)
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Benign
(Jan 29, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autoinflammatory syndrome
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002542775.1
First in ClinVar: Jul 09, 2022 Last updated: Jul 09, 2022 |
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Likely benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial hemophagocytic lymphohistiocytosis 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000644881.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
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Uncertain significance
(Jan 30, 2024)
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criteria provided, single submitter
Method: clinical testing
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PRF1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004120359.2
First in ClinVar: Nov 20, 2023 Last updated: Mar 16, 2024 |
Comment:
The PRF1 c.272C>T variant is predicted to result in the amino acid substitution p.Ala91Val. This variant has been studied extensively, but its clinical significance remains … (more)
The PRF1 c.272C>T variant is predicted to result in the amino acid substitution p.Ala91Val. This variant has been studied extensively, but its clinical significance remains unclear. The PRF1 gene variant c.272C>T is found at a high frequency among several control populations (up to 4.6% and in many homozygous individuals; and has been classified as a “neutral polymorphism” (Molleran Lee et al. 2004. PubMed ID: 14757862; Zur Stadt et al. 2004. PubMed ID: 15342365). However, considerable clinical and experimental data support a functional role of the p.Ala91Val variant resulting in reduced cytotoxic activity that may be significant for the pathogenesis of hemophagocytic lymphohistiocytosis and other disorders, including NK/T-Cell lymphomas, in both heterozygous and homozygous carriers of the p.Ala91Val substitution (Voskoboinik et al. 2005. PubMed ID: 15755897; Voskoboinik et al. 2007. PubMed ID: 17475905; Martínez-Pomar et al. 2013. PubMed ID: 23073290; Trambas et al. 2005. PubMed ID: 15741215; Clementi et al. 2002. PubMed ID: 12229880; Santoro et al. 2005. PubMed ID: 15921391; Zhang et al. 2011. PubMed ID: 21881043; Mancebo et al. 2006. PubMed ID: 16956828; House et al. 2015. PubMed ID: 25776844; Manso et al. 2014. PubMed ID: 24632576; Willig et al. 2015. PubMed ID: 25937001, Palterer et al. 2017. PubMed ID: 28863861). Consequently, this allele has also been categorized as either a functional polymorphism or as a risk allele. Due to conflicting reports, the significance of this variant remains uncertain. (less)
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Benign
(Mar 29, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000540113.1
First in ClinVar: Apr 09, 2017 Last updated: Apr 09, 2017 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (less)
Method: Genome/Exome Filtration
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Pathogenic
(Aug 26, 2014)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000280651.2
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Familial hemophagocytic lymphohistiocytosis 2
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001138067.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(Mar 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial hemophagocytic lymphohistiocytosis 2
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000363438.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Likely benign
(Jul 13, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002570677.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: PRF1 c.272C>T (p.Ala91Val) results in a non-conservative amino acid change located in the Membrane attack complex component/perforin (MACPF) domain (IPR020864) of the encoded … (more)
Variant summary: PRF1 c.272C>T (p.Ala91Val) results in a non-conservative amino acid change located in the Membrane attack complex component/perforin (MACPF) domain (IPR020864) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.029 in 280896 control chromosomes (gnomAD), predominantly at a frequency of 0.046 within the Non-Finnish European subpopulation in the gnomAD database, including 129 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 17 fold of the estimated maximal expected allele frequency for a pathogenic variant in PRF1 causing Familial Hemophagocytic Lymphohistiocytosis phenotype (0.0027), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. Experimental evidence using transiently transfected RBL-2H4 cells showed that the variant had approximately half the lytic activity as cells transfected with wild-type, which was further reduced to less than 10-fold activity when using purified A91V protein (Voskoboinik_2007). Primary natural killer cells from otherwise healthy heterozygous volunteers showed that natural killer cells from A91V/WT individuals had >35% reduction in cell killing efficiency compared with WT/WT individuals (House_2015). Six ClinVar submitters have assessed the variant since 2014: one classified the variant as pathogenic, two as likey benign, two as benign, and one as a risk factor. Based on the evidence outlined above, the variant was classified as likely benign. (less)
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Uncertain significance
(Mar 25, 2024)
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criteria provided, single submitter
Method: research
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Familial hemophagocytic lymphohistiocytosis 2
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004805429.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
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Uncertain significance
(Aug 15, 2007)
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no assertion criteria provided
Method: literature only
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RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000034974.5
First in ClinVar: Apr 04, 2013 Last updated: Sep 08, 2019 |
Comment on evidence:
This variant, formerly designated HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 2, SUSCEPTIBILITY TO, with 2 'included' designations, LYMPHOMA, NON-HODGKIN, SUSCEPTIBILITY TO and APLASTIC ANEMIA, SUSCEPTIBILITY TO, has been … (more)
This variant, formerly designated HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 2, SUSCEPTIBILITY TO, with 2 'included' designations, LYMPHOMA, NON-HODGKIN, SUSCEPTIBILITY TO and APLASTIC ANEMIA, SUSCEPTIBILITY TO, has been reclassified based on the reports by Molleran Lee et al. (2004), zur Stadt et al. (2004), and Lek et al. (2016). In 2 sibs with adult onset and atypical presentation of hemophagocytic lymphohistiocytosis (FHL2; 603553), Clementi et al. (2002) identified compound heterozygosity of a 272C-T transition in exon 2 of the PRF1 gene, resulting in an ala91-to-val (A91V) substitution, and a trp374-to-ter (W374X; 170280.0002) mutation in the PRF1 gene. Clementi et al. (2005) reported that 1 of the sibs had a non-Hodgkin lymphoma (605027). Busiello et al. (2004) reported a family in which fraternal twins were both homozygous for the A91V substitution but showed markedly different phenotypic expression. The proband presented at age 13 years with persistent fever, hepatosplenomegaly, cytopenia, and lymph node enlargement. Signs of hemophagocytosis in a liver biopsy specimen led to the diagnosis of FHL. The patient died after a rapidly progressive disease course. All the remaining family members, including the homozygous twin, were considered normal. Natural killer activity was severely impaired in the patient but normal in the asymptomatic twin. Both twins and the father carried a second PRF1 mutation in heterozygous state: 695G-A transition resulting in an R231H amino acid change. The report highlighted the long disease-free interval during which biochemical or immunologic alterations may not be evident and the suggestion that factors other than mutation in the perforin gene may be involved. Clementi et al. (2006) identified the A91V substitution of PRF1 in 6 of 28 patients with Dianzani autoimmune lymphoproliferative disease (DALD; 605233), a disorder that resembles autoimmune lymphoproliferative syndrome (ALPS; 601859) but lacks expansion of double-negative T cells. Presence of A91V conferred an odds ratio of 3 for DALD, and the odds ratio increased to 17 if variations in the osteopontin (SPP1; 166490) gene associated with increased osteopontin production were also present. However, A91V was relatively frequent (4.6%) in controls. Clementi et al. (2006) suggested that A91V may be a susceptibility factor for DALD in patients with defective FAS (TNFRSF6; 134637) function. Solomou et al. (2007) identified a heterozygous A91V substitution in 3 unrelated adults who developed aplastic anemia (609135) at ages 31, 77, and 78, respectively. Two of these patients had evidence of hemophagocytosis on bone marrow biopsy with no other clinical features of hemophagocytic syndrome. One patient had no response to immunosuppression, and 2 had only partial responses. Perforin protein levels and perforin granules were markedly decreased or absent in CD8(+) T cells. All 3 patients also carried a heterozygous synonymous his300-to-his (H300H) polymorphism in exon 3 of the PRF1 gene. The A91V substitution was identified in 24 (1.0%) of 2,312 control chromosomes. Molleran Lee et al. (2004) and zur Stadt et al. (2004) identified the A91V substitution with an allelic frequency of 3% and 9%, respectively, suggesting that it is a polymorphism. Lek et al. (2016) noted that the A211V (A91V) variant has a high allele frequency (0.0174) in the South Asian population in the ExAC database, suggesting that it is not pathogenic. Variant Function In rat basophil leukemia cells, Voskoboinik et al. (2005) found that the A91V PRF1 protein showed decreased expression, resulting in partial loss of lytic capacity. In studies of rat basophil leukemia cells and perforin-deficient mouse cytotoxic T cells, Voskoboinik et al. (2007) found that human A91V mutant protein had a 10-fold decrease in target cell lysis activity compared to wildtype protein. The mutant protein was also present at lower levels. Further studies suggested that the mutant protein undergoes abnormal folding. Voskoboinik et al. (2007) suggested that the diminished lytic activity of the A91V protein may be partly rescued by other granule toxins, thus resulting in a less dramatic clinical effect. (less)
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001550951.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The PRF1 p.Ala91Val variant was identified in the literature, however the role of its pathogenicity has been debated. The variant was identified in 15 of … (more)
The PRF1 p.Ala91Val variant was identified in the literature, however the role of its pathogenicity has been debated. The variant was identified in 15 of 320 proband chromosomes (frequency: 0.053) from individuals or families with haemophagocytic lymphohistiocytosis (HLH), acquired aplastic anemia, and Dianzani Autoimmune Lymphoproliferative Disease (Molleran_2004_PMID: 14757862, Solomou_2007_PMID: 17311987 & Clementi_2006_PMID: 16720836). The variant has also been reported in control population in multiple studies at frequencies of 0.046, 0.010, 0.0174 and 0.087 (Lek_2016_PMID: 27535533, Zur Stadt_2004_PMID: 15342365; Solomou_2007_PMID: 17311987 & Clementi_2006_PMID: 16720836). The variant was identified in dbSNP (ID: rs35947132) as “With Pathogenic allele”. In ClinVar, there are conflicting interpretations of pathogenicity from six submitters: 1x pathogenic (Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics), 2x likely benign (Illumina Clinical Services Laboratory and Invitae), 1x benign (Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine), and 2x uncertain significance (GeneDx and OMIM). The associated conditions are Hemophagocytic lymphohistiocytosis, familial, 2 and Familial hemophagocytic lymphohistiocytosis. The variant was also identified in LOVD 3.0 but was not found in Cosmic. The variant was identified in control databases in 8191 of 280896 chromosomes (171 homozygous) at a frequency of 0.02916 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 5912 of 128018 chromosomes (freq: 0.04618), Other in 252 of 7176 chromosomes (freq: 0.03512), Ashkenazi Jewish in 273 of 10298 chromosomes (freq: 0.02651), European (Finnish) in 655 of 24848 chromosomes (freq: 0.02636), Latino in 811 of 35320 chromosomes (freq: 0.02296), African in 153 of 24738 chromosomes (freq: 0.006185), South Asian in 132 of 30580 chromosomes (freq: 0.004317), and East Asian in 3 of 19918 chromosomes (freq: 0.000151). Perforin plays a key role in the cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). A functional study of the p.A91V variant showed that the variant resulted in impaired cleavage of perforin to its active form, resulting in loss of CTL and NK-cell cytotoxicity against targets (Trambas_2005_PMID: 15741215). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, and GeneSplicer) do not predict a difference in splicing. The p.Ala91 residue is not highly conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, and MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this varaint. This variant is classified as a variant of likely benign. (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002033872.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002036159.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Familial hemophagocytic lymphohistiocytosis 2
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV001976569.2
First in ClinVar: Oct 08, 2021 Last updated: Oct 01, 2022 |
Comment:
Variant assoc w/late-onset (adult) fHLH [Carvelli et al 2020, Miller et al 2020]. Common variant in population studies of healthy persons; functional effects were studied … (more)
Variant assoc w/late-onset (adult) fHLH [Carvelli et al 2020, Miller et al 2020]. Common variant in population studies of healthy persons; functional effects were studied [Chia et al 2009]. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Functional and genetic testing in adults with HLH reveals an inflammatory profile rather than a cytotoxicity defect. | Carvelli J | Blood | 2020 | PMID: 32356861 |
Identification of germline variants in adults with hemophagocytic lymphohistiocytosis. | Miller PG | Blood advances | 2020 | PMID: 32150605 |
Analysis of protein-coding genetic variation in 60,706 humans. | Lek M | Nature | 2016 | PMID: 27535533 |
Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity, delayed FHL, and a predisposition to cancer. | Chia J | Proceedings of the National Academy of Sciences of the United States of America | 2009 | PMID: 19487666 |
Perforin activity and immune homeostasis: the common A91V polymorphism in perforin results in both presynaptic and postsynaptic defects in function. | Voskoboinik I | Blood | 2007 | PMID: 17475905 |
Perforin gene mutations in patients with acquired aplastic anemia. | Solomou EE | Blood | 2007 | PMID: 17311987 |
Variations of the perforin gene in patients with autoimmunity/lymphoproliferation and defective Fas function. | Clementi R | Blood | 2006 | PMID: 16720836 |
A functional analysis of the putative polymorphisms A91V and N252S and 22 missense perforin mutations associated with familial hemophagocytic lymphohistiocytosis. | Voskoboinik I | Blood | 2005 | PMID: 15755897 |
A proportion of patients with lymphoma may harbor mutations of the perforin gene. | Clementi R | Blood | 2005 | PMID: 15728124 |
A91V is a polymorphism in the perforin gene not causative of an FHLH phenotype. | Zur Stadt U | Blood | 2004 | PMID: 15342365 |
Characterisation of diverse PRF1 mutations leading to decreased natural killer cell activity in North American families with haemophagocytic lymphohistiocytosis. | Molleran Lee S | Journal of medical genetics | 2004 | PMID: 14757862 |
Atypical features of familial hemophagocytic lymphohistiocytosis. | Busiello R | Blood | 2004 | PMID: 14739222 |
Adult onset and atypical presentation of hemophagocytic lymphohistiocytosis in siblings carrying PRF1 mutations. | Clementi R | Blood | 2002 | PMID: 12229880 |
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Text-mined citations for rs35947132 ...
HelpRecord last updated Apr 06, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.