11-747445-T-TCGC

Variant names:

• chr11-747445-T-TCGC
• rs71464113
• ENST00000319006.8:c.-21_-19dupCGC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The ENST00000319006.8(TALDO1):​c.-21_-19dupCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,511,032 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (8 hom.)
• Consequence: TALDO1 ENST00000319006.8 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -1.04
• 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, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0028 (425/151948) while in subpopulation SAS AF = 0.00456 (22/4820). AF 95% confidence interval is 0.00329. There are 1 homozygotes in GnomAd4. There are 201 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000319006.8. 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.-37_-36insCGC		upstream_gene	N/A	NP_006746.1	A0A140VK56

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TALDO1	ENST00000319006.8	TSL:1 MANE Select	c.-21_-19dupCGC		5_prime_UTR	Exon 1 of 8	ENSP00000321259.3	P37837-1
	TALDO1	ENST00000528097.5	TSL:1	c.-21_-19dupCGC		5_prime_UTR	Exon 1 of 8	ENSP00000437098.1	F2Z393
	TALDO1	ENST00000896396.1		c.-21_-19dupCGC		5_prime_UTR	Exon 1 of 9	ENSP00000566455.1

Frequencies

GnomAD3 genomes AF: 0.00278 AC: 422 AN: 151842 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00365

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.00305 AC: 377 AN: 123674 AF XY: 0.00343

Gnomad AFR exome AF: 0.000896

Gnomad AMR exome AF: 0.00323

Gnomad ASJ exome AF: 0.000280

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000364

Gnomad NFE exome AF: 0.00363

Gnomad OTH exome AF: 0.00345

GnomAD4 exome AF: 0.00299 AC: 4060 AN: 1359084 Hom.: 8 Cov.: 25 AF XY: 0.00308 AC XY: 2074 AN XY: 673068

African (AFR) AF: 0.00205 AC: 56 AN: 27334

American (AMR) AF: 0.00252 AC: 84 AN: 33382

Ashkenazi Jewish (ASJ) AF: 0.000167 AC: 4 AN: 23936

East Asian (EAS) AF: 0.000128 AC: 4 AN: 31288

South Asian (SAS) AF: 0.00467 AC: 357 AN: 76426

European-Finnish (FIN) AF: 0.000464 AC: 22 AN: 47378

Middle Eastern (MID) AF: 0.0106 AC: 59 AN: 5542

European-Non Finnish (NFE) AF: 0.00312 AC: 3305 AN: 1057660

Other (OTH) AF: 0.00301 AC: 169 AN: 56138

GnomAD4 genome AF: 0.00280 AC: 425 AN: 151948 Hom.: 1 Cov.: 33 AF XY: 0.00271 AC XY: 201 AN XY: 74280

African (AFR) AF: 0.00193 AC: 80 AN: 41506

American (AMR) AF: 0.00353 AC: 54 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5154

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4820

European-Finnish (FIN) AF: 0.000190 AC: 2 AN: 10514

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00367 AC: 249 AN: 67894

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00276

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Deficiency of transaldolase (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.0
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71464113; hg19: chr11-747445; COSMIC: COSV105899873; COSMIC: COSV105899873;