NM_000195.5(HPS1):c.198G>A (p.Ser66=) AND Hermansky-Pudlak syndrome 1

Clinical significance:Uncertain significance (Last evaluated: Jan 25, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000758238.2

Allele description [Variation Report for NM_000195.5(HPS1):c.198G>A (p.Ser66=)]

NM_000195.5(HPS1):c.198G>A (p.Ser66=)

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.198G>A (p.Ser66=)
HGVS:
  • NC_000010.11:g.98435692C>T
  • NG_009646.1:g.16256G>A
  • NM_000195.5:c.198G>AMANE SELECT
  • NM_001311345.1:c.-719G>A
  • NM_001322476.1:c.198G>A
  • NM_001322477.1:c.198G>A
  • NM_001322478.1:c.198G>A
  • NM_001322479.1:c.198G>A
  • NM_001322480.1:c.198G>A
  • NM_001322481.1:c.198G>A
  • NM_001322482.1:c.198G>A
  • NM_001322483.1:c.-29G>A
  • NM_001322484.1:c.-29G>A
  • NM_001322485.1:c.-29G>A
  • NM_001322487.1:c.-818G>A
  • NM_001322489.1:c.-576G>A
  • NM_001322490.1:c.198G>A
  • NM_001322491.1:c.198G>A
  • NM_001322492.1:c.198G>A
  • NM_182639.3:c.198G>A
  • NP_000186.2:p.Ser66=
  • NP_001309405.1:p.Ser66=
  • NP_001309406.1:p.Ser66=
  • NP_001309407.1:p.Ser66=
  • NP_001309408.1:p.Ser66=
  • NP_001309409.1:p.Ser66=
  • NP_001309410.1:p.Ser66=
  • NP_001309411.1:p.Ser66=
  • NP_001309419.1:p.Ser66=
  • NP_001309420.1:p.Ser66=
  • NP_001309421.1:p.Ser66=
  • NP_872577.1:p.Ser66=
  • LRG_562t1:c.198G>A
  • LRG_562:g.16256G>A
  • LRG_562p1:p.Ser66=
  • NC_000010.10:g.100195449C>T
  • NM_000195.3:c.198G>A
  • NM_000195.4:c.198G>A
Links:
dbSNP: rs115265574
NCBI 1000 Genomes Browser:
rs115265574
Molecular consequence:
  • NM_001311345.1:c.-719G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322483.1:c.-29G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322484.1:c.-29G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322485.1:c.-29G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322487.1:c.-818G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322489.1:c.-576G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000195.5:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001322476.1:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001322477.1:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001322478.1:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001322479.1:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001322480.1:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001322481.1:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001322482.1:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001322490.1:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001322491.1:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001322492.1:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_182639.3:c.198G>A - synonymous variant - [Sequence Ontology: SO:0001819]

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000886876Johns Hopkins Genomics, Johns Hopkins Universitycriteria provided, single submitter
Uncertain significance
(Jan 25, 2019)
germlineclinical testing

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

SCV001265832Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Jan 13, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV000886876.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This HPS1 variant (rs115265574) has been identified in large population datasets and the minor allele frequency is neither low enough to consider the variant rare (>0.1%) nor high enough to consider it a population polymorphism (>1%) within the African subpopulation (gnomAD: 84/24958 alleles; 0.34%, no homozygotes). A single submitter in ClinVar classifies this variant as uncertain clinical significance (Variation ID: 502551). This variant has not been reported in the literature, to our knowledge. Bioinformatic analysis predicts that this synonymous variant would not affect normal exon 4 splicing, although this has not been confirmed experimentally to our knowledge. Due to insufficient evidence that this variant is deleterious, the clinical significance of c.198G>A is uncertain at this time.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV001265832.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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