NM_000195.5(HPS1):c.972dup (p.Met325fs) AND Hermansky-Pudlak syndrome 1

Germline classification:: Pathogenic (10 submissions)
Last evaluated:: Feb 20, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000005596.19

Allele description [Variation Report for NM_000195.5(HPS1):c.972dup (p.Met325fs)]

NM_000195.5(HPS1):c.972dup (p.Met325fs)

Genes:

MIR4685:microRNA 4685 [Gene - HGNC]
HPS1:HPS1 biogenesis of lysosomal organelles complex 3 subunit 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

10q24.2

Genomic location:

Preferred name:

NM_000195.5(HPS1):c.972dup (p.Met325fs)

Other names:

p.Met325HisfsX128; NM_000195.5(HPS1):c.972dup; p.Met325fs

HGVS:

NC_000010.11:g.98427237dup
NG_009646.1:g.24718dup
NM_000195.5:c.972dupMANE SELECT
NM_001311345.2:c.-1dup
NM_001322476.2:c.972dup
NM_001322477.2:c.972dup
NM_001322478.2:c.873dup
NM_001322479.2:c.873dup
NM_001322480.2:c.711dup
NM_001322481.2:c.711dup
NM_001322482.2:c.612dup
NM_001322483.2:c.603dup
NM_001322484.2:c.603dup
NM_001322485.2:c.504dup
NM_001322487.2:c.-1dup
NM_001322489.2:c.-1dup
NP_000186.2:p.Met325fs
NP_001298274.1:p.Met1fs
NP_001309405.1:p.Met325fs
NP_001309406.1:p.Met325fs
NP_001309407.1:p.Met292fs
NP_001309408.1:p.Met292fs
NP_001309409.1:p.Met238fs
NP_001309410.1:p.Met238fs
NP_001309411.1:p.Met205fs
NP_001309412.1:p.Met202fs
NP_001309413.1:p.Met202fs
NP_001309414.1:p.Met169fs
NP_001309416.1:p.Met1fs
NP_001309418.1:p.Met1fs
LRG_562t1:c.972dup
LRG_562:g.24718dup
LRG_562p1:p.Met325fs
NC_000010.10:g.100186986_100186987insG
NC_000010.10:g.100186994dup
NM_000195.2:c.972dupC
NM_000195.3:c.972dup
NM_000195.3:c.972dupC
NM_000195.4:c.972dup
NM_000195.5:c.972dupCMANE SELECT

Protein change:

M169fs

Links:

OMIM: 604982.0002; dbSNP: rs281865082

NCBI 1000 Genomes Browser:

rs281865082

Molecular consequence:

NM_000195.5:c.972dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001311345.2:c.-1dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322476.2:c.972dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322477.2:c.972dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322478.2:c.873dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322479.2:c.873dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322480.2:c.711dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322481.2:c.711dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322482.2:c.612dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322483.2:c.603dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322484.2:c.603dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322485.2:c.504dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322487.2:c.-1dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322489.2:c.-1dup - frameshift variant - [Sequence Ontology: SO:0001589]

Functional consequence:

variation affecting RNA [Variation Ontology: 0297]

Observations:

Condition(s)

Name:: Hermansky-Pudlak syndrome 1 (HPS1)
Synonyms:: DELTA STORAGE POOL DISEASE
Identifiers:: MONDO: MONDO:0008748; MedGen: C2931875; Orphanet: 231500; Orphanet: 79430; OMIM: 203300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025778	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 1998)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 8274781, 8896559, 9497254
SCV000040539	GeneReviews	no classification provided	not provided	germline	literature only
SCV001161833	NIHR Bioresource Rare Diseases, University of Cambridge	no assertion criteria provided	Pathogenic	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV001440468	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 1, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001653247	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20301464, 9497254, 8896559, 31141302
SCV002025016	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002807102	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 12, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004013047	ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004199913	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 28, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004697331	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 20, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only
not provided	unknown	yes	1	not provided	not provided	1	not provided	clinical testing, research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hermansky-Pudlak syndrome in a Swiss population.

Schallreuter KU, Frenk E, Wolfe LS, Witkop CJ, Wood JM.

Dermatology. 1993;187(4):248-56.

PubMed [citation]

PMID:: 8274781

Whole-genome sequencing of patients with rare diseases in a national health system.

Turro E, Astle WJ, Megy K, Gräf S, Greene D, Shamardina O, Allen HL, Sanchis-Juan A, Frontini M, Thys C, Stephens J, Mapeta R, Burren OS, Downes K, Haimel M, Tuna S, Deevi SVV, Aitman TJ, Bennett DL, Calleja P, Carss K, Caulfield MJ, et al.

Nature. 2020 Jul;583(7814):96-102. doi: 10.1038/s41586-020-2434-2. Epub 2020 Jun 24.

PubMed [citation]

PMID:: 32581362
PMCID:: PMC7610553

See all PubMed Citations (7)

PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From OMIM, SCV000025778.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

In a patient from the inbred Swiss kindred with Hermansky-Pudlak syndrome (HPS1; 203300) studied by Schallreuter et al. (1993) and in an Irish-German HPS patient, Oh et al. (1996) identified homozygosity for a frameshift mutation due to an additional cytosine in a run of 8 cytosines in the HPS gene. Oh et al. (1998) reported this mutation as T322insC and found that the 2 patients were divergent for intragenic polymorphisms that flank the mutation; the findings suggested that the frameshift arose independently in the 2 populations. A French patient was found to be homozygous for the frameshift mutation and for the polymorphic haplotype found in the patient of Irish-German origin, and a Scottish patient was found to be compound heterozygous for the frameshift mutation with the haplotype found in the Irish-German patient and a novel glu666-to-ter (E666X; 604982.0003) nonsense mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneReviews, SCV000040539.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From NIHR Bioresource Rare Diseases, University of Cambridge, SCV001161833.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001440468.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV001653247.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	clinical testing	PubMed (4)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002025016.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002807102.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology, SCV004013047.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Baylor Genetics, SCV004199913.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV004697331.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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