rs756559860
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006440.5(TXNRD2):c.1436T>C(p.Leu479Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,613,356 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 (★★). Synonymous variant affecting the same amino acid position (i.e. L479L) has been classified as Likely benign.
Frequency
Consequence
NM_006440.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXNRD2 | NM_006440.5 | c.1436T>C | p.Leu479Pro | missense_variant | 16/18 | ENST00000400521.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNRD2 | ENST00000400521.7 | c.1436T>C | p.Leu479Pro | missense_variant | 16/18 | 1 | NM_006440.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248536Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135116
GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461120Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 726878
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74374
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 05, 2017 | This sequence change replaces leucine with proline at codon 479 of the TXNRD2 protein (p.Leu479Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs756559860, ExAC 0.003%) but has not been reported in the literature in individuals with a TXNRD2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 | Feb 21, 2023 | The p.L479P variant (also known as c.1436T>C), located in coding exon 16 of the TXNRD2 gene, results from a T to C substitution at nucleotide position 1436. The leucine at codon 479 is replaced by proline, 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 deleterious 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