3-126611041-T-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_052883.3(TXNRD3):c.1724A>T(p.Asp575Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000332 in 1,506,826 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D575Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_052883.3 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 |
---|---|---|---|---|---|---|---|
TXNRD3 | NM_052883.3 | c.1724A>T | p.Asp575Val | missense_variant | 14/16 | ENST00000524230.9 | |
TXNRD3 | NM_001173513.3 | c.1616A>T | p.Asp539Val | missense_variant | 13/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNRD3 | ENST00000524230.9 | c.1724A>T | p.Asp575Val | missense_variant | 14/16 | 1 | NM_052883.3 | P1 | |
TXNRD3 | ENST00000523403.3 | c.1616A>T | p.Asp539Val | missense_variant | 13/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000295 AC: 4AN: 1354602Hom.: 0 Cov.: 25 AF XY: 0.00000299 AC XY: 2AN XY: 668020
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.1724A>T (p.D575V) alteration is located in exon 14 (coding exon 14) of the TXNRD3 gene. This alteration results from a A to T substitution at nucleotide position 1724, causing the aspartic acid (D) at amino acid position 575 to be replaced by a valine (V). 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