rs762695606
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006440.5(TXNRD2):āc.589C>Gā(p.His197Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,461,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. H197H) has been classified as Likely benign.
Frequency
Consequence
NM_006440.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXNRD2 | NM_006440.5 | c.589C>G | p.His197Asp | missense_variant, splice_region_variant | 7/18 | ENST00000400521.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNRD2 | ENST00000400521.7 | c.589C>G | p.His197Asp | missense_variant, splice_region_variant | 7/18 | 1 | NM_006440.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248060Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134646
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461468Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 726962
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2020 | This sequence change replaces histidine with aspartic acid at codon 197 of the TXNRD2 protein (p.His197Asp). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and aspartic acid. This variant is not present in population databases (ExAC no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TXNRD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 454285). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at