rs730882052
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_001231.5(CASQ1):c.731A>G(p.Asp244Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. D244D) has been classified as Likely benign.
Frequency
Consequence
NM_001231.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASQ1 | NM_001231.5 | c.731A>G | p.Asp244Gly | missense_variant | 6/11 | ENST00000368078.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASQ1 | ENST00000368078.8 | c.731A>G | p.Asp244Gly | missense_variant | 6/11 | 1 | NM_001231.5 | P1 | |
CASQ1 | ENST00000481081.1 | n.616A>G | non_coding_transcript_exon_variant | 5/8 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Myopathy due to calsequestrin and SERCA1 protein overload Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2014 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CASQ1 function (PMID: 25116801, 26416891). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 183021). This missense change has been observed in individuals with CASQ1-related myopathy (PMID: 25116801). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 244 of the CASQ1 protein (p.Asp244Gly). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at