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NM_000195.5(HPS1):c.1096C>A (p.Pro366Thr) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 4, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:

Allele description [Variation Report for NM_000195.5(HPS1):c.1096C>A (p.Pro366Thr)]

NM_000195.5(HPS1):c.1096C>A (p.Pro366Thr)

HPS1:HPS1 biogenesis of lysosomal organelles complex 3 subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000195.5(HPS1):c.1096C>A (p.Pro366Thr)
Other names:
NM_000195.5(HPS1):c.1096C>A; p.Pro366Thr
  • NC_000010.11:g.98425877G>T
  • NG_009646.1:g.26071C>A
  • NM_000195.5:c.1096C>AMANE SELECT
  • NM_001311345.2:c.124C>A
  • NM_001322476.2:c.1096C>A
  • NM_001322477.2:c.1096C>A
  • NM_001322478.2:c.997C>A
  • NM_001322479.2:c.997C>A
  • NM_001322480.2:c.835C>A
  • NM_001322481.2:c.835C>A
  • NM_001322482.2:c.736C>A
  • NM_001322483.2:c.727C>A
  • NM_001322484.2:c.727C>A
  • NM_001322485.2:c.628C>A
  • NM_001322487.2:c.124C>A
  • NM_001322489.2:c.124C>A
  • NP_000186.2:p.Pro366Thr
  • NP_001298274.1:p.Pro42Thr
  • NP_001309405.1:p.Pro366Thr
  • NP_001309406.1:p.Pro366Thr
  • NP_001309407.1:p.Pro333Thr
  • NP_001309408.1:p.Pro333Thr
  • NP_001309409.1:p.Pro279Thr
  • NP_001309410.1:p.Pro279Thr
  • NP_001309411.1:p.Pro246Thr
  • NP_001309412.1:p.Pro243Thr
  • NP_001309413.1:p.Pro243Thr
  • NP_001309414.1:p.Pro210Thr
  • NP_001309416.1:p.Pro42Thr
  • NP_001309418.1:p.Pro42Thr
  • LRG_562t1:c.1096C>A
  • LRG_562:g.26071C>A
  • LRG_562p1:p.Pro366Thr
  • NC_000010.10:g.100185634G>T
  • NM_000195.3:c.1096C>A
  • NM_000195.4:c.1096C>A
Protein change:
dbSNP: rs138771756
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000195.5:c.1096C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001311345.2:c.124C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322476.2:c.1096C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322477.2:c.1096C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322478.2:c.997C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322479.2:c.997C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322480.2:c.835C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322481.2:c.835C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322482.2:c.736C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322483.2:c.727C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322484.2:c.727C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322485.2:c.628C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322487.2:c.124C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322489.2:c.124C>A - missense variant - [Sequence Ontology: SO:0001583]


MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV002765963Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(Nov 4, 2022)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders.

Downes K, Megy K, Duarte D, Vries M, Gebhart J, Hofer S, Shamardina O, Deevi SVV, Stephens J, Mapeta R, Tuna S, Al Hasso N, Besser MW, Cooper N, Daugherty L, Gleadall N, Greene D, Haimel M, Martin H, Papadia S, Revel-Vilk S, Sivapalaratnam S, et al.

Blood. 2019 Dec 5;134(23):2082-2091. doi: 10.1182/blood.2018891192.

PubMed [citation]

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002765963.1

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


Variant summary: HPS1 c.1096C>A (p.Pro366Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251426 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1096C>A has been reported in the literature in an individual affected with a platelet function disorder who was a compound heterozygote with another pathogenic/likely pathogenic variant (Downes_2019). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Mar 30, 2024