rs727502867

Variant names:

• chr11-763901-GC-G
• rs727502867
• NM_006755.2:c.793delC

Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_006755.2(TALDO1):​c.793delC​(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
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:6
• Conservation: PhyloP100: 4.27
• Publications: 2 publications found

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]

TALDO1 Gene-Disease associations (from GenCC):

• transaldolase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Pathogenic. The variant received 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 VariationId is 162622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TALDO1	NM_006755.2	c.793delC	p.Gln265ArgfsTer56	frameshift_variant	Exon 6 of 8	ENST00000319006.8	NP_006746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TALDO1	ENST00000319006.8	c.793delC	p.Gln265ArgfsTer56	frameshift_variant	Exon 6 of 8	1	NM_006755.2	ENSP00000321259.3
TALDO1	ENST00000528097.5	c.793delC	p.Gln265ArgfsTer17	frameshift_variant	Exon 6 of 8	1		ENSP00000437098.1
TALDO1	ENST00000530666.1	n.-80delC		upstream_gene_variant		2
TALDO1	ENST00000530440.1	n.*452delC		downstream_gene_variant		3		ENSP00000433501.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of transaldolase Pathogenic:5

Sep 26, 2019

Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 06, 2021

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 19, 2019

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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] -

Nov 01, 2013

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Mar 26, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Pathogenic:1

Aug 18, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 162622). This premature translational stop signal has been observed in individual(s) with transaldolase deficiency (PMID: 23315216; Invitae). This variant is not present in population databases (ExAC no frequency). 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3
Mutation Taster		=8/192	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs727502867; hg19: chr11-763901;