rs1008642
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PS1PM1PP3_StrongPP5_Moderate
The NM_033337.3(CAV3):c.99C>A(p.Asn33Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar. Synonymous variant affecting the same amino acid position (i.e. N33N) has been classified as Likely benign.
Frequency
Consequence
NM_033337.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAV3 | NM_033337.3 | c.99C>A | p.Asn33Lys | missense_variant | 1/2 | ENST00000343849.3 | |
CAV3 | NM_001234.5 | c.99C>A | p.Asn33Lys | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAV3 | ENST00000343849.3 | c.99C>A | p.Asn33Lys | missense_variant | 1/2 | 1 | NM_033337.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1452968Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 723392
GnomAD4 genome ? Cov.: 30
ClinVar
Submissions by phenotype
Long QT syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 27, 2022 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 457133). This variant is also known as p.Asn32Lys. This missense change has been observed in individuals with autosomal dominant CAV3-related conditions (PMID: 15564037, 15580566, 27061274, 31127727). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 33 of the CAV3 protein (p.Asn33Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at