22-36476744-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_012473.4(TXN2):āc.376A>Gā(p.Ile126Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_012473.4 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 |
---|---|---|---|---|---|---|---|
TXN2 | NM_012473.4 | c.376A>G | p.Ile126Val | missense_variant | 3/4 | ENST00000216185.7 | |
TXN2 | XM_006724226.2 | c.376A>G | p.Ile126Val | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXN2 | ENST00000216185.7 | c.376A>G | p.Ile126Val | missense_variant | 3/4 | 1 | NM_012473.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251460Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135906
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727246
GnomAD4 genome AF: 0.000125 AC: 19AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74322
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2022 | The c.376A>G (p.I126V) alteration is located in exon 3 (coding exon 2) of the TXN2 gene. This alteration results from a A to G substitution at nucleotide position 376, causing the isoleucine (I) at amino acid position 126 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Combined oxidative phosphorylation deficiency 29 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 27, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2023 | 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: 1031205). This variant has not been reported in the literature in individuals affected with TXN2-related conditions. This variant is present in population databases (rs141470075, gnomAD 0.04%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 126 of the TXN2 protein (p.Ile126Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at