rs147774793
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000070.3(CAPN3):c.2235C>A(p.Tyr745Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,754 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 (★★). Synonymous variant affecting the same amino acid position (i.e. Y745Y) has been classified as Likely benign. 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 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN3 | NM_000070.3 | c.2235C>A | p.Tyr745Ter | stop_gained | 21/24 | ENST00000397163.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN3 | ENST00000397163.8 | c.2235C>A | p.Tyr745Ter | stop_gained | 21/24 | 1 | NM_000070.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151954Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461800Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727192
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151954Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74200
ClinVar
Submissions by phenotype
Muscular dystrophy, limb-girdle, autosomal dominant 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 24, 2023 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2A Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 09, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 499202). This premature translational stop signal has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 15689361). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr745*) 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). - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 27, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at