NM_000195.5(HPS1):c.759C>G (p.Asp253Glu) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 16, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002632536.3

Allele description [Variation Report for NM_000195.5(HPS1):c.759C>G (p.Asp253Glu)]

NM_000195.5(HPS1):c.759C>G (p.Asp253Glu)

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.759C>G (p.Asp253Glu)

HGVS:

NC_000010.11:g.98430580G>C
NG_009646.1:g.21368C>G
NM_000195.5:c.759C>GMANE SELECT
NM_001311345.2:c.-115C>G
NM_001322476.2:c.759C>G
NM_001322477.2:c.759C>G
NM_001322478.2:c.759C>G
NM_001322479.2:c.759C>G
NM_001322480.2:c.498C>G
NM_001322481.2:c.498C>G
NM_001322482.2:c.498C>G
NM_001322483.2:c.390C>G
NM_001322484.2:c.390C>G
NM_001322485.2:c.390C>G
NM_001322487.2:c.-214C>G
NM_001322489.2:c.-115C>G
NM_001322490.2:c.641C>G
NM_001322491.2:c.759C>G
NM_001322492.2:c.641C>G
NM_182639.4:c.759C>G
NP_000186.2:p.Asp253Glu
NP_001309405.1:p.Asp253Glu
NP_001309406.1:p.Asp253Glu
NP_001309407.1:p.Asp253Glu
NP_001309408.1:p.Asp253Glu
NP_001309409.1:p.Asp166Glu
NP_001309410.1:p.Asp166Glu
NP_001309411.1:p.Asp166Glu
NP_001309412.1:p.Asp130Glu
NP_001309413.1:p.Asp130Glu
NP_001309414.1:p.Asp130Glu
NP_001309419.1:p.Thr214Arg
NP_001309420.1:p.Asp253Glu
NP_001309421.1:p.Thr214Arg
NP_872577.1:p.Asp253Glu
LRG_562t1:c.759C>G
LRG_562:g.21368C>G
LRG_562p1:p.Asp253Glu
NC_000010.10:g.100190337G>C

Protein change:

D130E

Molecular consequence:

NM_001311345.2:c.-115C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322487.2:c.-214C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322489.2:c.-115C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000195.5:c.759C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322476.2:c.759C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322477.2:c.759C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322478.2:c.759C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322479.2:c.759C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322480.2:c.498C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322481.2:c.498C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322482.2:c.498C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322483.2:c.390C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322484.2:c.390C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322485.2:c.390C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322490.2:c.641C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322491.2:c.759C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322492.2:c.641C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_182639.4:c.759C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003503558	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 16, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003503558

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 16, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003503558.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with HPS1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 253 of the HPS1 protein (p.Asp253Glu).

#	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: Sep 29, 2024

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