10-73998227-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014000.3(VCL):c.20G>A(p.Arg7His) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,474 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 (★★).
Frequency
Consequence
NM_014000.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246722Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134130
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460474Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726472
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1W Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 1378723). This variant has not been reported in the literature in individuals affected with VCL-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine with histidine at codon 7 of the VCL protein (p.Arg7His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. -
Cardiovascular phenotype Uncertain:1
The p.R7H variant (also known as c.20G>A), located in coding exon 1 of the VCL gene, results from a G to A substitution at nucleotide position 20. The arginine at codon 7 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at