rs200202503
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 5P and 4B. PVS1_StrongPP5BS2
The NM_033337.3(CAV3):c.294C>A(p.Cys98Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,854 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_033337.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAV3 | NM_033337.3 | c.294C>A | p.Cys98Ter | stop_gained | 2/2 | ENST00000343849.3 | |
CAV3 | NM_001234.5 | c.294C>A | p.Cys98Ter | stop_gained | 2/3 | ||
OXTR | XR_007095681.1 | n.1885-3103G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAV3 | ENST00000343849.3 | c.294C>A | p.Cys98Ter | stop_gained | 2/2 | 1 | NM_033337.3 | P1 | |
CAV3 | ENST00000397368.2 | c.294C>A | p.Cys98Ter | stop_gained | 2/3 | 1 | P1 | ||
CAV3 | ENST00000472766.1 | n.155+11715C>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461854Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727232
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | AiLife Diagnostics, AiLife Diagnostics | Aug 24, 2021 | - - |
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Long QT syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 31, 2019 | This sequence change results in a premature translational stop signal in the CAV3 gene (p.Cys98*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 54 amino acids of the CAV3 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) unselected for cardiac conditions undergoing exome sequencing (PMID: 23861362). ClinVar contains an entry for this variant (Variation ID: 191444). This variant disrupts the p.Pro105 amino acid residue in CAV3. Other variants that disrupt this residue have been determined to be pathogenic (PMID: 9537420,18509671, 19238754, 21182936, 28232187, 30153853). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at