chr22-19877127-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006440.5(TXNRD2):c.1553C>T(p.Thr518Met) variant causes a missense change. The variant allele was found at a frequency of 0.00013 in 1,600,740 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T518T) 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.1553C>T | p.Thr518Met | missense_variant | 17/18 | ENST00000400521.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNRD2 | ENST00000400521.7 | c.1553C>T | p.Thr518Met | missense_variant | 17/18 | 1 | NM_006440.5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152106Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000105 AC: 26AN: 246632Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 134398
GnomAD4 exome AF: 0.000137 AC: 198AN: 1448514Hom.: 0 Cov.: 31 AF XY: 0.000150 AC XY: 108AN XY: 718192
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74432
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 28, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function - |
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 518 of the TXNRD2 protein (p.Thr518Met). This variant is present in population databases (rs372446673, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TXNRD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1775101). 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 2023 | The p.T518M variant (also known as c.1553C>T), located in coding exon 17 of the TXNRD2 gene, results from a C to T substitution at nucleotide position 1553. The threonine at codon 518 is replaced by methionine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at