chr15-42394305-G-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000070.3(CAPN3):c.1079G>A(p.Trp360Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,411,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000070.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN3 | NM_000070.3 | c.1079G>A | p.Trp360Ter | stop_gained | 8/24 | ENST00000397163.8 | |
CAPN3 | NM_024344.2 | c.1079G>A | p.Trp360Ter | stop_gained | 8/23 | ||
CAPN3 | NM_173087.2 | c.935G>A | p.Trp312Ter | stop_gained | 7/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN3 | ENST00000397163.8 | c.1079G>A | p.Trp360Ter | stop_gained | 8/24 | 1 | NM_000070.3 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000213 AC: 3AN: 1411074Hom.: 0 Cov.: 31 AF XY: 0.00000430 AC XY: 3AN XY: 697144
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2A Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2021 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 550578). This premature translational stop signal has been observed in individual(s) with autosomal recessive CAPN3-related conditions (PMID: 7720071). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp360*) in the CAPN3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CAPN3 are known to be pathogenic (PMID: 10330340, 15689361). - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Feb 01, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 20, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at