22-19877158-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006440.5(TXNRD2):c.1522C>T(p.Arg508Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,609,832 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. R508H) has been classified as Likely benign.
Frequency
Consequence
NM_006440.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXNRD2 | NM_006440.5 | c.1522C>T | p.Arg508Cys | missense_variant | 17/18 | ENST00000400521.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNRD2 | ENST00000400521.7 | c.1522C>T | p.Arg508Cys | missense_variant | 17/18 | 1 | NM_006440.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152066Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000283 AC: 7AN: 247722Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134910
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1457766Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 724640
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152066Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74284
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 10, 2021 | This sequence change replaces arginine with cysteine at codon 508 of the TXNRD2 protein (p.Arg508Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with TXNRD2-related conditions. This variant is present in population databases (rs368176907, ExAC 0.01%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at