rs797045110
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006755.2(TALDO1):c.516dupC(p.Ala173fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TALDO1
NM_006755.2 frameshift
NM_006755.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.302
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 12 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 11-763397-T-TC is Pathogenic according to our data. Variant chr11-763397-T-TC is described in ClinVar as [Pathogenic]. Clinvar id is 208617.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TALDO1 | NM_006755.2 | c.516dupC | p.Ala173fs | frameshift_variant | 5/8 | ENST00000319006.8 | NP_006746.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TALDO1 | ENST00000319006.8 | c.516dupC | p.Ala173fs | frameshift_variant | 5/8 | 1 | NM_006755.2 | ENSP00000321259.3 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD3 genomes
Cov.:
30
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461586Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 727108
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727108
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GnomAD4 genome Cov.: 30
GnomAD4 genome
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30
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Deficiency of transaldolase Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 30, 2014 | The p.Ala173ArgfsX23 variant in TALDO1 has not been previously reported in individuals with disease and data from large population studies is insufficient to assess the frequency of this variant. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 173 and leads to a premature termination codon 23 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Biallelic loss of function variants in TALDO1 have been shown to cause transaldolase deficiency. In summary, this variant meets our criteria to be classified as pathogenic for transaldolase deficiency in an autosomal recessive manner. - |
Computational scores
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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