chr22-36476827-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_012473.4(TXN2):c.293C>T(p.Pro98Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000867 in 1,613,860 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. P98P) has been classified as Likely benign.
Frequency
Consequence
NM_012473.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXN2 | NM_012473.4 | c.293C>T | p.Pro98Leu | missense_variant | 3/4 | ENST00000216185.7 | |
TXN2 | XM_006724226.2 | c.293C>T | p.Pro98Leu | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXN2 | ENST00000216185.7 | c.293C>T | p.Pro98Leu | missense_variant | 3/4 | 1 | NM_012473.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000724 AC: 11AN: 151974Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251480Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135914
GnomAD4 exome AF: 0.0000882 AC: 129AN: 1461886Hom.: 0 Cov.: 33 AF XY: 0.0000866 AC XY: 63AN XY: 727242
GnomAD4 genome AF: 0.0000724 AC: 11AN: 151974Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74190
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 04, 2022 | This variant has not been reported in the literature in individuals affected with TXN2-related conditions. 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 disruptive. This variant is present in population databases (rs139984170, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 98 of the TXN2 protein (p.Pro98Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at