ClinVar Genomic variation as it relates to human health
NM_000195.5(HPS1):c.1189del (p.Gln397fs)
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
-
NM_000195.5(HPS1):c.1189del (p.Gln397fs)
Variation ID: 21091 Accession: VCV000021091.33
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 10q24.2 10: 98425687 (GRCh38) [ NCBI UCSC ] 10: 100185444 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 28, 2024 Feb 20, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000195.5:c.1189del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000186.2:p.Gln397fs frameshift NM_000195.4:c.1189del NM_001311345.2:c.217del NP_001298274.1:p.Gln73fs frameshift NM_001322476.2:c.1189del NP_001309405.1:p.Gln397fs frameshift NM_001322477.2:c.1189del NP_001309406.1:p.Gln397fs frameshift NM_001322478.2:c.1090del NP_001309407.1:p.Gln364fs frameshift NM_001322479.2:c.1090del NP_001309408.1:p.Gln364fs frameshift NM_001322480.2:c.928del NP_001309409.1:p.Gln310fs frameshift NM_001322481.2:c.928del NP_001309410.1:p.Gln310fs frameshift NM_001322482.2:c.829del NP_001309411.1:p.Gln277fs frameshift NM_001322483.2:c.820del NP_001309412.1:p.Gln274fs frameshift NM_001322484.2:c.820del NP_001309413.1:p.Gln274fs frameshift NM_001322485.2:c.721del NP_001309414.1:p.Gln241fs frameshift NM_001322487.2:c.217del NP_001309416.1:p.Gln73fs frameshift NM_001322489.2:c.217del NP_001309418.1:p.Gln73fs frameshift NC_000010.11:g.98425689del NC_000010.10:g.100185446del NG_009646.1:g.26261del LRG_562:g.26261del LRG_562t1:c.1189del LRG_562p1:p.Gln397fs - Protein change
- Q241fs, Q310fs, Q364fs, Q274fs, Q277fs, Q397fs, Q73fs
- Other names
- NM_000195.5(HPS1):c.1189del
- p.Gln397fs
- Canonical SPDI
- NC_000010.11:98425686:GGG:GG
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
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
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (3) |
criteria provided, single submitter
|
Jan 29, 2024 | RCV000796076.9 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Nov 29, 2021 | RCV000851664.4 | |
Pathogenic/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
|
Feb 20, 2024 | RCV000020181.19 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Feb 01, 2019)
|
criteria provided, single submitter
Method: research
|
Hermansky-Pudlak syndrome
Affected status: yes
Allele origin:
unknown
|
NIHR Bioresource Rare Diseases, University of Cambridge
Study: ThromboGenomics
Accession: SCV000899448.1 First in ClinVar: Sep 29, 2019 Last updated: Sep 29, 2019 |
Sex: female
Ethnicity/Population group: European
|
|
Pathogenic
(Apr 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hermansky-Pudlak syndrome 1
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002810326.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Jul 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hermansky-Pudlak syndrome 1
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002025014.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000935571.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln397Serfs*2) 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.Gln397Serfs*2) 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 (rs281865084, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with HPS1-related conditions (PMID: 9497254, 20514622, 28081892). This variant is also known as E397delC. ClinVar contains an entry for this variant (Variation ID: 21091). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Nov 29, 2021)
|
criteria provided, single submitter
Method: curation
|
Hermansky-Pudlak syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV002097057.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
Comment:
The p.Gln397fs variant in HPS1 has been reported in at least 9 individuals with Hermansky-Pudlak syndrome (PMID: 31619213, 26806224, 28081892, 20514622, 9497254, 15952982), segregated with … (more)
The p.Gln397fs variant in HPS1 has been reported in at least 9 individuals with Hermansky-Pudlak syndrome (PMID: 31619213, 26806224, 28081892, 20514622, 9497254, 15952982), segregated with disease in 2 affected relatives from 2 families (PMID: 20514622) and has been identified in 0.01% (19/128472) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs281865084). Although this variant has been seen in the general population in a heterozygous state, its frequency is not high enough to rule out a pathogenic role. This variant has also been reported in ClinVar (Variation ID#: 21091) and has been interpreted as Likely Pathogenic or Pathogenic by Illumina Clinical Services Laboratory (Illumina), Centre for Mendelian Genomics (University Medical Centre Ljubljana), NIHR Bioresource Rare Diseases (University of Cambridge), Invitae, and GeneReviews. Of the at least 9 affected individuals, 2 of those were homozygotes, and 1 were compound heterozygote that carried a reported likely pathogenic variants in trans, which increases the likelihood that the p.Gln397fs variant is pathogenic (PMID: 17365864, 9497254, 20514622). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 397 and leads to a premature termination codon 2 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, PVS1, PP1_moderate (Richards 2015). (less)
|
|
Likely pathogenic
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hermansky-Pudlak syndrome 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000359659.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The HPS1 c.1189delC (p.Gln397SerfsTer2) variant results in a frameshift and is predicted to cause a premature termination of the protein. The variant is reported in … (more)
The HPS1 c.1189delC (p.Gln397SerfsTer2) variant results in a frameshift and is predicted to cause a premature termination of the protein. The variant is reported in six studies in which it is found in a total of nine out of 43 individuals with Hermansky-Pudlak syndrome (HPS), including two homozygotes, one hemizygote, and six compound heterozygotes, and in four unaffected heterozygous family members (Oh et al. 1998; Shotelersuk et al. 1998; Griffin et al. 2005; Huizing et al. 2007; Sandrock et al. 2010; Westmoreland et al. 2016). Control data are unavailable for this variant, which is reported at a frequency of 0.00012 in the European (non-Finnish) population of the Exome Aggregation Consortium. Northern blot analysis of fibroblasts from the hemizygous individual showed significantly reduced HPS RNA (Shotelersuk et al. 1998). Based on the collective evidence, the p.Gln397SerfsTer2 variant is classified as pathogenic for Hermansky-Pudlak syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
|
|
Pathogenic
(Sep 16, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hermansky-Pudlak syndrome 1
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001367002.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2,PM3,PP4. This variant was detected in homozygous state.
|
|
Pathogenic
(Oct 21, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hermansky-Pudlak syndrome 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004199919.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Pathogenic
(Feb 20, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hermansky-Pudlak syndrome 1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV004697332.1
First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024 |
Clinical Features:
Macrocephaly (present) , Albinism (present) , Ocular albinism (present)
|
|
Pathogenic
(Jul 24, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Hermansky-Pudlak syndrome
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002076663.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001924301.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001973170.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: research
|
Hermansky-Pudlak syndrome 1
Affected status: yes
Allele origin:
unknown
|
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology
Accession: SCV002515570.1
First in ClinVar: May 21, 2022 Last updated: May 21, 2022
Comment:
Submitted to GoldVariant by Harald Schulze from Institute of Experimental Biomedicine, University Hospital of Würzburg, Würzburg, Germany
|
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Hermansky-Pudlak syndrome 1
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV000040514.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
Hermansky-Pudlak Syndrome. | Adam MP | - | 2023 | PMID: 20301464 |
Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders. | Downes K | Blood | 2019 | PMID: 31064749 |
Rapid Resolution of Blended or Composite Multigenic Disease in Infants by Whole-Exome Sequencing. | Theunissen TEJ | The Journal of pediatrics | 2017 | PMID: 28081892 |
Super-resolution microscopy as a potential approach to diagnosis of platelet granule disorders. | Westmoreland D | Journal of thrombosis and haemostasis : JTH | 2016 | PMID: 26806224 |
Compound heterozygous mutations in 2 siblings with Hermansky-Pudlak syndrome type 1 (HPS1). | Sandrock K | Klinische Padiatrie | 2010 | PMID: 20514622 |
Platelet alpha granules in BLOC-2 and BLOC-3 subtypes of Hermansky-Pudlak syndrome. | Huizing M | Platelets | 2007 | PMID: 17365864 |
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 |
Detection of hemizygosity in Hermansky-Pudlak syndrome by quantitative real-time PCR. | Griffin AE | Clinical genetics | 2005 | PMID: 15952982 |
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 |
Three new mutations in a gene causing Hermansky-Pudlak syndrome: clinical correlations. | Shotelersuk V | Molecular genetics and metabolism | 1998 | PMID: 9705234 |
Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity. | Oh J | American journal of human genetics | 1998 | PMID: 9497254 |
click to load more click to collapse |
Text-mined citations for rs281865084 ...
HelpRecord last updated May 08, 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.