chr22-19941716-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006440.5(TXNRD2):c.88G>T(p.Ala30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000808 in 1,484,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict 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. A30A) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXNRD2 | NM_006440.5 | c.88G>T | p.Ala30Ser | missense_variant | 1/18 | ENST00000400521.7 | |
TXNRD2 | NM_001352300.2 | c.88G>T | p.Ala30Ser | missense_variant | 1/17 | ||
TXNRD2 | NM_001282512.3 | c.88G>T | p.Ala30Ser | missense_variant | 1/12 | ||
TXNRD2 | NR_147957.2 | n.103G>T | non_coding_transcript_exon_variant | 1/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNRD2 | ENST00000400521.7 | c.88G>T | p.Ala30Ser | missense_variant | 1/18 | 1 | NM_006440.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152086Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000825 AC: 11AN: 1332692Hom.: 0 Cov.: 31 AF XY: 0.00000913 AC XY: 6AN XY: 657228
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152086Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2022 | 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. ClinVar contains an entry for this variant (Variation ID: 577326). This variant has not been reported in the literature in individuals affected with TXNRD2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 30 of the TXNRD2 protein (p.Ala30Ser). - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 29, 2022 | The c.88G>T (p.A30S) alteration is located in exon 1 (coding exon 1) of the TXNRD2 gene. This alteration results from a G to T substitution at nucleotide position 88, causing the alanine (A) at amino acid position 30 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at