rs1060502316
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_033337.3(CAV3):c.431A>G(p.Lys144Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_033337.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAV3 | NM_033337.3 | c.431A>G | p.Lys144Arg | missense_variant | 2/2 | ENST00000343849.3 | |
CAV3 | NM_001234.5 | c.431A>G | p.Lys144Arg | missense_variant | 2/3 | ||
OXTR | XR_007095681.1 | n.1885-3240T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAV3 | ENST00000343849.3 | c.431A>G | p.Lys144Arg | missense_variant | 2/2 | 1 | NM_033337.3 | P1 | |
CAV3 | ENST00000397368.2 | c.431A>G | p.Lys144Arg | missense_variant | 2/3 | 1 | P1 | ||
CAV3 | ENST00000472766.1 | n.155+11852A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460780Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726652
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74314
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 04, 2017 | A variant of uncertain significance has been identified in the CAV3 gene. The K144R variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). However, the K144R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to lysine (K) are tolerated across species and where arginine (R) is present as the wild type in multiple species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 27, 2019 | - - |
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 144 of the CAV3 protein (p.Lys144Arg). This variant is present in population databases (no rsID available, gnomAD 0.1%). 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: 409258). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at