11-747445-TCGCCGCCGCCGC-T

Position:

• chr11-747445-TCGCCGCCGCCGC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000528097.5(TALDO1):​c.-30_-19del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00866 in 1,511,000 control chromosomes in the GnomAD database, including 75 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0089 (71 hom.)
• Consequence: TALDO1 ENST00000528097.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.357

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 11-747445-TCGCCGCCGCCGC-T is Benign according to our data. Variant chr11-747445-TCGCCGCCGCCGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 306085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00675 (1025/151950) while in subpopulation NFE AF= 0.0101 (683/67894). AF 95% confidence interval is 0.00943. There are 4 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 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: 0.00676 AC: 1026 AN: 151844 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00675

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00694

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00753 AC: 931 AN: 123674 Hom.: 2 AF XY: 0.00737 AC XY: 509 AN XY: 69020

Gnomad AFR exome AF: 0.00119

Gnomad AMR exome AF: 0.00369

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000631

Gnomad FIN exome AF: 0.00772

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.00972

GnomAD4 exome AF: 0.00888 AC: 12062 AN: 1359050 Hom.: 71 AF XY: 0.00862 AC XY: 5801 AN XY: 673052

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.00404

Gnomad4 ASJ exome AF: 0.0143

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000536

Gnomad4 FIN exome AF: 0.00735

Gnomad4 NFE exome AF: 0.0101

Gnomad4 OTH exome AF: 0.00809

GnomAD4 genome AF: 0.00675 AC: 1025 AN: 151950 Hom.: 4 Cov.: 33 AF XY: 0.00639 AC XY: 475 AN XY: 74280

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00674

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00694

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00299 Hom.: 0

Bravo AF: 0.00651

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deficiency of transaldolase Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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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;