rs751425603
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM2PM5PP3_StrongPP5_Very_Strong
The NM_006755.2(TALDO1):c.574C>T(p.Arg192Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000428 in 1,613,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R192H) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006755.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TALDO1 | NM_006755.2 | c.574C>T | p.Arg192Cys | missense_variant | 5/8 | ENST00000319006.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TALDO1 | ENST00000319006.8 | c.574C>T | p.Arg192Cys | missense_variant | 5/8 | 1 | NM_006755.2 | P1 | |
TALDO1 | ENST00000528097.5 | c.574C>T | p.Arg192Cys | missense_variant | 5/8 | 1 | |||
TALDO1 | ENST00000528070.5 | c.*572C>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/6 | 5 | ||||
TALDO1 | ENST00000530440.1 | c.*233C>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151538Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251442Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135908
GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461866Hom.: 0 Cov.: 35 AF XY: 0.0000454 AC XY: 33AN XY: 727238
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151538Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 73952
ClinVar
Submissions by phenotype
Deficiency of transaldolase Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 15, 2020 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg192 amino acid residue in TALDO1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15877206, 24497183, 29292491). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 381759). This missense change has been observed in individual(s) with transaldolase deficiency (PMID: 18331807, 25388407). This variant is present in population databases (rs751425603, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 192 of the TALDO1 protein (p.Arg192Cys). - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 11, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18331807, 25388407, 27391121, 23315216, 27130472, 35186000, 30740741, 32828637, 37071763, 34677006, 31769880) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at