chr11-747445-T-TCGC

Position:

• chr11-747445-T-TCGC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The ENST00000528097.5(TALDO1):​c.-21_-19dup 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 ENST00000528097.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TALDO1	NM_006755.2			upstream_gene_variant		ENST00000319006.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TALDO1	ENST00000319006.8			upstream_gene_variant		1	NM_006755.2	P1

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

GnomAD3 exomes AF: 0.00305 AC: 377 AN: 123674 Hom.: 3 AF XY: 0.00343 AC XY: 237 AN XY: 69020

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 SAS exome AF: 0.00552

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

Gnomad4 AFR exome AF: 0.00205

Gnomad4 AMR exome AF: 0.00252

Gnomad4 ASJ exome AF: 0.000167

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.00467

Gnomad4 FIN exome AF: 0.000464

Gnomad4 NFE exome AF: 0.00312

Gnomad4 OTH exome AF: 0.00301

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

Gnomad4 AFR AF: 0.00193

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.00367

Gnomad4 OTH AF: 0.00663

Bravo AF: 0.00276

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of transaldolase Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71464113; hg19: chr11-747445;