NM_000195.5(HPS1):c.9C>A (p.Cys3Ter) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 8, 2023
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:: RCV001822003.5

Allele description

NM_000195.5(HPS1):c.9C>A (p.Cys3Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

10q24.2

Genomic location:

Preferred name:

NM_000195.5(HPS1):c.9C>A (p.Cys3Ter)

HGVS:

NC_000010.11:g.98443232G>T
NG_009646.1:g.8716C>A
NM_000195.5:c.9C>AMANE SELECT
NM_001311345.2:c.-908C>A
NM_001322476.2:c.9C>A
NM_001322477.2:c.9C>A
NM_001322478.2:c.9C>A
NM_001322479.2:c.9C>A
NM_001322480.2:c.9C>A
NM_001322481.2:c.9C>A
NM_001322482.2:c.9C>A
NM_001322483.2:c.-218C>A
NM_001322484.2:c.-218C>A
NM_001322485.2:c.-218C>A
NM_001322487.2:c.-1007C>A
NM_001322489.2:c.-765C>A
NM_001322490.2:c.9C>A
NM_001322491.2:c.9C>A
NM_001322492.2:c.9C>A
NM_182639.4:c.9C>A
NP_000186.2:p.Cys3Ter
NP_001309405.1:p.Cys3Ter
NP_001309406.1:p.Cys3Ter
NP_001309407.1:p.Cys3Ter
NP_001309408.1:p.Cys3Ter
NP_001309409.1:p.Cys3Ter
NP_001309410.1:p.Cys3Ter
NP_001309411.1:p.Cys3Ter
NP_001309419.1:p.Cys3Ter
NP_001309420.1:p.Cys3Ter
NP_001309421.1:p.Cys3Ter
NP_872577.1:p.Cys3Ter
LRG_562t1:c.9C>A
LRG_562:g.8716C>A
LRG_562p1:p.Cys3Ter
NC_000010.10:g.100202989G>T
NM_000195.3:c.9C>A
NM_000195.4:c.9C>A

Protein change:

C3*

Links:

dbSNP: rs750909242

NCBI 1000 Genomes Browser:

rs750909242

Molecular consequence:

NM_001311345.2:c.-908C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322483.2:c.-218C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322484.2:c.-218C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322485.2:c.-218C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322487.2:c.-1007C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322489.2:c.-765C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000195.5:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322476.2:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322477.2:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322478.2:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322479.2:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322480.2:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322481.2:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322482.2:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322490.2:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322491.2:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322492.2:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_182639.4:c.9C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens MHC class II antigen (HLA-DRB1) mRNA, HLA-DRB1*12:02:01 allele, com...
Homo sapiens MHC class II antigen (HLA-DRB1) mRNA, HLA-DRB1*12:02:01 allele, complete cds
gi|298162286|gb|HM067854.1|

Nucleotide
nuclear pore complex protein Nup93 isoform 2 [Mus musculus]
nuclear pore complex protein Nup93 isoform 2 [Mus musculus]
gi|2581665055|ref|NP_001411375.1|

Protein
Xenopus tropicalis embryo gastrula
Xenopus tropicalis embryo gastrula

biosample
BioSample links for Nucleotide (Select 119037765) (1)
BioSample

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002067349	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 3, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004436092	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12442288, 16185271, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002067349

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 3, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004436092

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 8, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Hermansky-Pudlak syndrome type 1: gene organization, novel mutations, and clinical-molecular review of non-Puerto Rican cases.

Hermos CR, Huizing M, Kaiser-Kupfer MI, Gahl WA.

Hum Mutat. 2002 Dec;20(6):482.

PubMed [citation]

PMID:: 12442288

See all PubMed Citations (4)

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002067349.1

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

Description

The c.9C>A sequence change results in the creation of a premature stop codon at amino acid position 3, p.Cys3*. This sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated HPS1 protein with potentially abnormal function. This pathogenic sequence change has not been described in patients with HPS1-related disorders. It has not been observed in the population databases (ExAC and gnomAD). These collective evidences indicate that this sequence change is likely pathogenic.

#	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

From Invitae, SCV004436092.1

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

Description

This sequence change creates a premature translational stop signal (p.Cys3*) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HPS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1324541). For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Jun 17, 2024

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