chr15-42359815-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000070.3(CAPN3):c.10G>A(p.Val4Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000148 in 1,613,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V4V) has been classified as Likely benign.
Frequency
Consequence
NM_000070.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.10G>A | p.Val4Ile | missense_variant | 1/24 | ENST00000397163.8 | |
CAPN3 | NM_024344.2 | c.10G>A | p.Val4Ile | missense_variant | 1/23 | ||
CAPN3 | NM_173087.2 | c.10G>A | p.Val4Ile | missense_variant | 1/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN3 | ENST00000397163.8 | c.10G>A | p.Val4Ile | missense_variant | 1/24 | 1 | NM_000070.3 | P2 | |
CAPN3 | ENST00000357568.8 | c.10G>A | p.Val4Ile | missense_variant | 1/23 | 1 | |||
CAPN3 | ENST00000349748.8 | c.10G>A | p.Val4Ile | missense_variant | 1/21 | 1 | |||
CAPN3 | ENST00000318023.11 | c.10G>A | p.Val4Ile | missense_variant | 1/23 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000160 AC: 40AN: 250370Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135734
GnomAD4 exome AF: 0.000157 AC: 229AN: 1461410Hom.: 0 Cov.: 32 AF XY: 0.000177 AC XY: 129AN XY: 727020
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74298
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2A Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 21, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 4 of the CAPN3 protein (p.Val4Ile). This variant is present in population databases (rs140660066, gnomAD 0.04%). This missense change has been observed in individual(s) with autosomal recessive limb girdle muscular dystrophy, type 2A (PMID: 10330340). ClinVar contains an entry for this variant (Variation ID: 468640). 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. - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 14, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 20, 2017 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2A;C4748295:Muscular dystrophy, limb-girdle, autosomal dominant 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 09, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at