ClinVar Genomic variation as it relates to human health
NM_000195.5(HPS1):c.355del (p.His119fs)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000195.5(HPS1):c.355del (p.His119fs)
Variation ID: 21103 Accession: VCV000021103.17
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 10q24.2 10: 98435315 (GRCh38) [ NCBI UCSC ] 10: 100195072 (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 Apr 4, 2013 Feb 14, 2024 Dec 14, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000195.5:c.355del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000186.2:p.His119fs frameshift NM_000195.5:c.355delC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000195.3:c.355del NM_001311345.2:c.-562del 5 prime UTR NM_001322476.2:c.355del NP_001309405.1:p.His119fs frameshift NM_001322477.2:c.355del NP_001309406.1:p.His119fs frameshift NM_001322478.2:c.355del NP_001309407.1:p.His119fs frameshift NM_001322479.2:c.355del NP_001309408.1:p.His119fs frameshift NM_001322480.2:c.255+320del intron variant NM_001322481.2:c.255+320del intron variant NM_001322482.2:c.255+320del intron variant NM_001322483.2:c.29+320del intron variant NM_001322484.2:c.29+320del intron variant NM_001322485.2:c.29+320del intron variant NM_001322487.2:c.-661del 5 prime UTR NM_001322489.2:c.-519+320del intron variant NM_001322490.2:c.355del NP_001309419.1:p.His119fs frameshift NM_001322491.2:c.355del NP_001309420.1:p.His119fs frameshift NM_001322492.2:c.355del NP_001309421.1:p.His119fs frameshift NM_182639.4:c.355del NP_872577.1:p.His119fs frameshift NC_000010.11:g.98435315del NC_000010.10:g.100195072del NG_009646.1:g.16633del LRG_562:g.16633del LRG_562t1:c.355del LRG_562p1:p.His119fs - Protein change
- H119fs
- Other names
- NM_000195.5(HPS1):c.355del
- p.His119fs
- Canonical SPDI
- NC_000010.11:98435314:G:
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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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
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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HPS1 | - | - |
GRCh38 GRCh37 |
1086 | 1118 |
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
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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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Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 26, 2023 | RCV000020193.7 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 14, 2023 | RCV001067590.8 | |
Pathogenic (2) |
criteria provided, single submitter
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Nov 29, 2021 | RCV001275007.3 |
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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Pathogenic
(Nov 29, 2021)
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criteria provided, single submitter
Method: curation
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Hermansky-Pudlak syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV002097066.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
Comment:
The p.His119fs variant in HPS1 has been reported in 3 individuals with Hermansky-Pudlak syndrome (PMID: 12442288, 20514622, DOI: 10.26502/acmcr.96550313) and has been identified in 0.002% … (more)
The p.His119fs variant in HPS1 has been reported in 3 individuals with Hermansky-Pudlak syndrome (PMID: 12442288, 20514622, DOI: 10.26502/acmcr.96550313) and has been identified in 0.002% (3/129066) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs281865075). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 21103) and has been interpreted as pathogenic by Invitae, Natera, Inc., and GeneReviews. Of the 3 affected individuals, all were compound heterozygotes that carried a reported pathogenic variant in trans or with unknown phase, which increases the likelihood that the p.His119fs variant is pathogenic (VariationID: 21091; PMID: 12442288, 20514622, DOI: 10.26502/acmcr.96550313). In vitro functional studies provide some evidence that the p.His119fs variant may slightly impact protein function (PMID: 12442288). However, these types of assays may not accurately represent biological function. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 119 and leads to a premature termination codon 5 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the HPS1 gene is an established disease mechanism in autosomal recessive Hermansky-Pudlak syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Hermansky-Pudlak syndrome. ACMG/AMP Criteria applied: PM3_strong, PM2_supporting, PVS1, PS3_supporting (Richards 2015). (less)
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Pathogenic
(May 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hermansky-Pudlak syndrome 1
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV001752682.2
First in ClinVar: Jul 18, 2021 Last updated: Dec 31, 2022 |
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Pathogenic
(Oct 17, 2022)
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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: SCV003918401.1
First in ClinVar: Apr 23, 2023 Last updated: Apr 23, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31589614, 31898847, 20514622, 12442288, Boeckelmann2020[paper]) (less)
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Pathogenic
(Oct 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hermansky-Pudlak syndrome 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004199914.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001232658.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.His119Thrfs*5) in the HPS1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.His119Thrfs*5) in the HPS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HPS1 are known to be pathogenic (PMID: 12442288, 16185271). This variant is present in population databases (rs281865075, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Hermansky-Pudlak syndrome (PMID: 12442288). This variant is also known as c.561delC. ClinVar contains an entry for this variant (Variation ID: 21103). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Hermansky-Pudlak syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001459683.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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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High frequency of Hermansky-Pudlak syndrome type 1 (HPS1) among Japanese albinism patients and functional analysis of HPS1 mutant protein. | Ito S | The Journal of investigative dermatology | 2005 | PMID: 16185271 |
Hermansky-Pudlak syndrome type 1: gene organization, novel mutations, and clinical-molecular review of non-Puerto Rican cases. | Hermos CR | Human mutation | 2002 | PMID: 12442288 |
Text-mined citations for rs281865075 ...
HelpRecord last updated Mar 30, 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.