rs140425651
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM1PP3BP4_StrongBP6
The NM_000070.3(CAPN3):c.2071G>A(p.Gly691Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000874 in 1,612,362 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. G691G) has been classified as Likely benign.
Frequency
Consequence
NM_000070.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN3 | NM_000070.3 | c.2071G>A | p.Gly691Arg | missense_variant | 19/24 | ENST00000397163.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN3 | ENST00000397163.8 | c.2071G>A | p.Gly691Arg | missense_variant | 19/24 | 1 | NM_000070.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152070Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.000195 AC: 49AN: 251388Hom.: 1 AF XY: 0.000177 AC XY: 24AN XY: 135866
GnomAD4 exome AF: 0.0000760 AC: 111AN: 1460174Hom.: 0 Cov.: 34 AF XY: 0.0000661 AC XY: 48AN XY: 726338
GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152188Hom.: 1 Cov.: 31 AF XY: 0.000188 AC XY: 14AN XY: 74390
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2A Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 17, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 691 of the CAPN3 protein (p.Gly691Arg). This variant is present in population databases (rs140425651, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with CAPN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 281011). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CAPN3 protein function. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 29, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 16, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at