rs727502867
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_006755.2(TALDO1):c.793del(p.Gln265ArgfsTer56) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
TALDO1
NM_006755.2 frameshift
NM_006755.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.27
Genes affected
TALDO1 (HGNC:11559): (transaldolase 1) Transaldolase 1 is a key enzyme of the nonoxidative pentose phosphate pathway providing ribose-5-phosphate for nucleic acid synthesis and NADPH for lipid biosynthesis. This pathway can also maintain glutathione at a reduced state and thus protect sulfhydryl groups and cellular integrity from oxygen radicals. The functional gene of transaldolase 1 is located on chromosome 11 and a pseudogene is identified on chromosome 1 but there are conflicting map locations. The second and third exon of this gene were developed by insertion of a retrotransposable element. This gene is thought to be involved in multiple sclerosis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-763901-GC-G is Pathogenic according to our data. Variant chr11-763901-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 162622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TALDO1 | NM_006755.2 | c.793del | p.Gln265ArgfsTer56 | frameshift_variant | 6/8 | ENST00000319006.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TALDO1 | ENST00000319006.8 | c.793del | p.Gln265ArgfsTer56 | frameshift_variant | 6/8 | 1 | NM_006755.2 | P1 | |
TALDO1 | ENST00000528097.5 | c.793del | p.Gln265ArgfsTer17 | frameshift_variant | 6/8 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Deficiency of transaldolase Pathogenic:5
Pathogenic, no assertion criteria provided | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Sep 26, 2019 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 06, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 19, 2019 | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 23315216] - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2013 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2021 | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln265Argfs*56) in the TALDO1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 73 amino acid(s) of the TALDO1 protein. This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with transaldolase deficiency (PMID: 23315216; Invitae). ClinVar contains an entry for this variant (Variation ID: 162622). - |
Computational scores
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Calibrated prediction
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at