rs374523166
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2
The NM_033337.3(CAV3):c.109G>C(p.Val37Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000252 in 1,590,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. V37A) has been classified as Uncertain significance.
Frequency
Consequence
NM_033337.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAV3 | NM_033337.3 | c.109G>C | p.Val37Leu | missense_variant | 1/2 | ENST00000343849.3 | |
CAV3 | NM_001234.5 | c.109G>C | p.Val37Leu | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAV3 | ENST00000343849.3 | c.109G>C | p.Val37Leu | missense_variant | 1/2 | 1 | NM_033337.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152040Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250832Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135626
GnomAD4 exome AF: 0.0000236 AC: 34AN: 1438154Hom.: 0 Cov.: 26 AF XY: 0.0000265 AC XY: 19AN XY: 717082
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152040Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74268
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 23, 2023 | Observed in patient with prolonged QT in the literature (Ye et al., 2020); Variant shown to impact protein function and localization compared to wildtype (Ye et al., 2020); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32634502, 32387251, 25630502) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 12, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 28, 2019 | - - |
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 06, 2023 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 37 of the CAV3 protein (p.Val37Leu). This variant is present in population databases (rs374523166, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CAV3-related conditions. ClinVar contains an entry for this variant (Variation ID: 96239). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 31, 2019 | The c.109G>C (p.V37L) alteration is located in exon 1 (coding exon 1) of the CAV3 gene. This alteration results from a G to C substitution at nucleotide position 109, causing the valine (V) at amino acid position 37 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at