chr15-42359846-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000070.3(CAPN3):c.41C>T(p.Ala14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A14E) has been classified as Uncertain significance.
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.41C>T | p.Ala14Val | missense_variant | 1/24 | ENST00000397163.8 | |
CAPN3 | NM_024344.2 | c.41C>T | p.Ala14Val | missense_variant | 1/23 | ||
CAPN3 | NM_173087.2 | c.41C>T | p.Ala14Val | missense_variant | 1/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN3 | ENST00000397163.8 | c.41C>T | p.Ala14Val | missense_variant | 1/24 | 1 | NM_000070.3 | P2 | |
CAPN3 | ENST00000357568.8 | c.41C>T | p.Ala14Val | missense_variant | 1/23 | 1 | |||
CAPN3 | ENST00000349748.8 | c.41C>T | p.Ala14Val | missense_variant | 1/21 | 1 | |||
CAPN3 | ENST00000318023.11 | c.41C>T | p.Ala14Val | missense_variant | 1/23 | 5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152222Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250564Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135740
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461752Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727164
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 02, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 06, 2020 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 05, 2019 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2A Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 12, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 14 of the CAPN3 protein (p.Ala14Val). This variant is present in population databases (rs771263688, gnomAD 0.004%). 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: 500229). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at