ENST00000528097.5:c.-30C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000528097.5(TALDO1):​c.-30C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,505,960 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0016 (6 hom.)
• Consequence: TALDO1 ENST00000528097.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.970
• Publications: 1 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: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000999 (150/150182) while in subpopulation AMR AF = 0.00398 (60/15076). AF 95% confidence interval is 0.00317. There are 0 homozygotes in GnomAd4. There are 70 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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>T		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>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000437098.1	F2Z393
	TALDO1	ENST00000528097.5	TSL:1	c.-30C>T		5_prime_UTR	Exon 1 of 8	ENSP00000437098.1	F2Z393
	TALDO1	ENST00000896396.1		c.-30C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000566455.1

Frequencies

GnomAD3 genomes AF: 0.00100 AC: 150 AN: 150072 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00105

Gnomad OTH AF: 0.00491

GnomAD2 exomes AF: 0.000858 AC: 128 AN: 149258 AF XY: 0.000844

Gnomad AFR exome AF: 0.000217

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000124

Gnomad FIN exome AF: 0.0000609

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.00106

GnomAD4 exome AF: 0.00159 AC: 2161 AN: 1355778 Hom.: 6 Cov.: 29 AF XY: 0.00154 AC XY: 1034 AN XY: 672090

African (AFR) AF: 0.000468 AC: 13 AN: 27758

American (AMR) AF: 0.00269 AC: 93 AN: 34548

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

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

South Asian (SAS) AF: 0.000181 AC: 14 AN: 77392

European-Finnish (FIN) AF: 0.000147 AC: 7 AN: 47468

Middle Eastern (MID) AF: 0.000537 AC: 3 AN: 5584

European-Non Finnish (NFE) AF: 0.00187 AC: 1969 AN: 1051578

Other (OTH) AF: 0.00111 AC: 62 AN: 56050

GnomAD4 genome AF: 0.000999 AC: 150 AN: 150182 Hom.: 0 Cov.: 34 AF XY: 0.000953 AC XY: 70 AN XY: 73458

African (AFR) AF: 0.000217 AC: 9 AN: 41422

American (AMR) AF: 0.00398 AC: 60 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3362

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00105 AC: 70 AN: 66628

Other (OTH) AF: 0.00486 AC: 10 AN: 2058

Alfa AF: 0.000971 Hom.: 0

Bravo AF: 0.00111

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Deficiency of transaldolase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.0
DANN	Benign	0.86
PhyloP100		-0.97
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs373293125; hg19: chr11-747452;