rs527236030
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_ModeratePP5_Moderate
The NM_001382567.1(STIM1):c.343A>T(p.Ile115Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I115T) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001382567.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STIM1 | NM_001382567.1 | c.343A>T | p.Ile115Phe | missense_variant | 3/13 | ENST00000526596.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STIM1 | ENST00000526596.2 | c.343A>T | p.Ile115Phe | missense_variant | 3/13 | 5 | NM_001382567.1 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Undiagnosed Diseases Program Translational Research Laboratory, National Institutes of Health | - | - - |
Myopathy with tubular aggregates;C1861451:Stormorken syndrome;C2748557:Combined immunodeficiency due to STIM1 deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 06, 2020 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant has been reported to be de novo in individuals affected with tubular aggregate myopathy and York platelet syndrome (YPS) and segregates in a family affected with YPS (PMID: 24570283, 25577287). ClinVar contains an entry for this variant (Variation ID: 143191). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with phenylalanine at codon 115 of the STIM1 protein (p.Ile115Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. - |
Myopathy, tubular aggregate, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2015 | - - |
Stormorken syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at