11-747452-C-G

Variant names:

• chr11-747452-C-G
• rs373293125
• ENST00000528097.5:c.-30C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000528097.5(TALDO1):​c.-30C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TALDO1 ENST00000528097.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970
• Publications: 0 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, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000528097.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TALDO1	NM_006755.2	MANE Select	c.-30C>G		upstream_gene	N/A	NP_006746.1	A0A140VK56

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TALDO1	ENST00000528097.5	TSL:1	c.-30C>G		5_prime_UTR	Exon 1 of 8	ENSP00000437098.1	F2Z393
	TALDO1	ENST00000896396.1		c.-30C>G		5_prime_UTR	Exon 1 of 9	ENSP00000566455.1
	TALDO1	ENST00000933599.1		c.-30C>G		5_prime_UTR	Exon 1 of 8	ENSP00000603658.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355784 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 672094

African (AFR) AF: 0.00 AC: 0 AN: 27758

American (AMR) AF: 0.00 AC: 0 AN: 34552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23528

East Asian (EAS) AF: 0.00 AC: 0 AN: 31872

South Asian (SAS) AF: 0.00 AC: 0 AN: 77392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 9.51e-7 AC: 1 AN: 1051580

Other (OTH) AF: 0.00 AC: 0 AN: 56050

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		-0.97
PromoterAI		-0.10	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs373293125;

hg19: chr11-747452;