NM_001382567.1(STIM1):c.488C>A (p.Ala163Asp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 18, 2023
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:: RCV000541355.12

Allele description [Variation Report for NM_001382567.1(STIM1):c.488C>A (p.Ala163Asp)]

NM_001382567.1(STIM1):c.488C>A (p.Ala163Asp)

Gene:

STIM1:stromal interaction molecule 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_001382567.1(STIM1):c.488C>A (p.Ala163Asp)

Other names:

p.Ala163Asp

HGVS:

NC_000011.10:g.4055628C>A
NG_016277.1:g.204926C>A
NM_001277961.3:c.488C>A
NM_001277962.2:c.488C>A
NM_001382566.1:c.266C>A
NM_001382567.1:c.488C>AMANE SELECT
NM_001382568.1:c.488C>A
NM_001382569.1:c.353C>A
NM_001382570.1:c.386-14398C>A
NM_001382571.1:c.18-3653C>A
NM_001382572.1:c.488C>A
NM_001382573.1:c.266C>A
NM_001382574.1:c.266C>A
NM_001382575.1:c.266C>A
NM_001382576.1:c.266C>A
NM_001382577.1:c.266C>A
NM_001382578.1:c.266C>A
NM_001382579.1:c.266C>A
NM_001382580.1:c.-2C>A
NM_001382581.1:c.-2C>A
NM_003156.4:c.488C>A
NP_001264890.1:p.Ala163Asp
NP_001264891.1:p.Ala163Asp
NP_001369495.1:p.Ala89Asp
NP_001369496.1:p.Ala163Asp
NP_001369497.1:p.Ala163Asp
NP_001369498.1:p.Ala118Asp
NP_001369501.1:p.Ala163Asp
NP_001369502.1:p.Ala89Asp
NP_001369503.1:p.Ala89Asp
NP_001369504.1:p.Ala89Asp
NP_001369505.1:p.Ala89Asp
NP_001369506.1:p.Ala89Asp
NP_001369507.1:p.Ala89Asp
NP_001369508.1:p.Ala89Asp
NP_003147.2:p.Ala163Asp
NP_003147.2:p.Ala163Asp
LRG_164t1:c.488C>A
LRG_164:g.204926C>A
LRG_164p1:p.Ala163Asp
NC_000011.9:g.4076858C>A
NM_003156.3:c.488C>A
NR_168436.1:n.1095C>A
NR_168437.1:n.1095C>A
NR_168438.1:n.1095C>A

Protein change:

A118D

Links:

dbSNP: rs199893056

NCBI 1000 Genomes Browser:

rs199893056

Molecular consequence:

NM_001382580.1:c.-2C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001382581.1:c.-2C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001382570.1:c.386-14398C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001382571.1:c.18-3653C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001277961.3:c.488C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001277962.2:c.488C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382566.1:c.266C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382567.1:c.488C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382568.1:c.488C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382569.1:c.353C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382572.1:c.488C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382573.1:c.266C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382574.1:c.266C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382575.1:c.266C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382576.1:c.266C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382577.1:c.266C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382578.1:c.266C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382579.1:c.266C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003156.4:c.488C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_168436.1:n.1095C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_168437.1:n.1095C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_168438.1:n.1095C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Stormorken syndrome (STRMK)
Synonyms:: THROMBOCYTOPATHY, ASPLENIA, AND MIOSIS
Identifiers:: MONDO: MONDO:0008497; MedGen: C1861451; Orphanet: 3204; OMIM: 185070

Name:: Combined immunodeficiency due to STIM1 deficiency
Synonyms:: Immune dysfunction with T-cell inactivation due to calcium entry defect 2; STIM1 DEFICIENCY; IMMUNODEFICIENCY 10
Identifiers:: MONDO: MONDO:0013008; MedGen: C2748557; Orphanet: 169090; Orphanet: 317430; OMIM: 612783

Name:: Myopathy with tubular aggregates (TAM)
Synonyms:: Tubular Aggregate Myopathy
Identifiers:: MONDO: MONDO:0008051; MedGen: C0410207; OMIM: PS160565

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000634553	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 18, 2023)	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

SCV000634553

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 18, 2023)

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, SCV000634553.8

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 163 of the STIM1 protein (p.Ala163Asp). This variant is present in population databases (rs199893056, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with STIM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 461735). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt STIM1 protein function with a positive predictive value of 80%. 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.

#	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: Oct 20, 2024

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