rs727503838
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000070.3(CAPN3):c.1354G>C(p.Asp452His) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. 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. D452G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000070.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN3 | NM_000070.3 | c.1354G>C | p.Asp452His | missense_variant, splice_region_variant | 10/24 | ENST00000397163.8 | |
CAPN3 | NM_024344.2 | c.1354G>C | p.Asp452His | missense_variant, splice_region_variant | 10/23 | ||
CAPN3 | NM_173087.2 | c.1210G>C | p.Asp404His | missense_variant, splice_region_variant | 9/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN3 | ENST00000397163.8 | c.1354G>C | p.Asp452His | missense_variant, splice_region_variant | 10/24 | 1 | NM_000070.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Muscular dystrophy, limb-girdle, autosomal dominant 4 Pathogenic:1
Likely pathogenic, flagged submission | clinical testing | Baylor Genetics | Jun 15, 2022 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Aug 22, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at