chr22-19880713-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006440.5(TXNRD2):c.1091G>A(p.Arg364Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000391 in 1,609,492 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R364L) has been classified as Uncertain significance.
Frequency
Consequence
NM_006440.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000134 AC: 2AN: 148712Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000607 AC: 15AN: 247144Hom.: 0 AF XY: 0.0000742 AC XY: 10AN XY: 134786
GnomAD4 exome AF: 0.0000418 AC: 61AN: 1460668Hom.: 0 Cov.: 35 AF XY: 0.0000523 AC XY: 38AN XY: 726658
GnomAD4 genome AF: 0.0000134 AC: 2AN: 148824Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 2AN XY: 72764
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TXNRD2 protein function. ClinVar contains an entry for this variant (Variation ID: 572761). This variant has not been reported in the literature in individuals affected with TXNRD2-related conditions. This variant is present in population databases (rs199734322, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 364 of the TXNRD2 protein (p.Arg364Gln). -
Cardiovascular phenotype Uncertain:1
The p.R364Q variant (also known as c.1091G>A), located in coding exon 13 of the TXNRD2 gene, results from a G to A substitution at nucleotide position 1091. The arginine at codon 364 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly 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