15-42359818-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000070.3(CAPN3):c.13A>G(p.Ile5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000070.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN3 | NM_000070.3 | c.13A>G | p.Ile5Val | missense_variant | 1/24 | ENST00000397163.8 | |
CAPN3 | NM_024344.2 | c.13A>G | p.Ile5Val | missense_variant | 1/23 | ||
CAPN3 | NM_173087.2 | c.13A>G | p.Ile5Val | missense_variant | 1/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN3 | ENST00000397163.8 | c.13A>G | p.Ile5Val | missense_variant | 1/24 | 1 | NM_000070.3 | P2 | |
CAPN3 | ENST00000357568.8 | c.13A>G | p.Ile5Val | missense_variant | 1/23 | 1 | |||
CAPN3 | ENST00000349748.8 | c.13A>G | p.Ile5Val | missense_variant | 1/21 | 1 | |||
CAPN3 | ENST00000318023.11 | c.13A>G | p.Ile5Val | missense_variant | 1/23 | 5 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250410Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135748
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461512Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727074
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2021 | This sequence change replaces isoleucine with valine at codon 5 of the CAPN3 protein (p.Ile5Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CAPN3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at