chr7-35202471-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001077653.2(TBX20):c.1303G>A(p.Gly435Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,606,062 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 Uncertain significance (★★).
Frequency
Consequence
NM_001077653.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151904Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000213 AC: 5AN: 235134Hom.: 0 AF XY: 0.0000236 AC XY: 3AN XY: 127236
GnomAD4 exome AF: 0.0000303 AC: 44AN: 1454158Hom.: 0 Cov.: 33 AF XY: 0.0000263 AC XY: 19AN XY: 722566
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151904Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74204
ClinVar
Submissions by phenotype
not provided Uncertain:1
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 disruptive. 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. ClinVar contains an entry for this variant (Variation ID: 1446987). This variant has not been reported in the literature in individuals affected with TBX20-related conditions. This variant is present in population databases (rs777607652, gnomAD 0.005%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 435 of the TBX20 protein (p.Gly435Arg). -
Cardiovascular phenotype Uncertain:1
The p.G435R variant (also known as c.1303G>A), located in coding exon 8 of the TBX20 gene, results from a G to A substitution at nucleotide position 1303. The glycine at codon 435 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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