chr11-747445-TCGCCGCCGCCGC-T

Variant names:

• chr11-747445-TCGCCGCCGCCGC-T
• rs71464113
• ENST00000528097.5:c.-30_-19delCGCCGCCGCCGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000528097.5(TALDO1):​c.-30_-19delCGCCGCCGCCGC 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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• 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: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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.-36_-25delCGCCGCCGCCGC		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.-30_-19delCGCCGCCGCCGC		5_prime_UTR	Exon 1 of 8	ENSP00000437098.1	F2Z393
	TALDO1	ENST00000896396.1		c.-30_-19delCGCCGCCGCCGC		5_prime_UTR	Exon 1 of 9	ENSP00000566455.1
	TALDO1	ENST00000933599.1		c.-30_-19delCGCCGCCGCCGC		5_prime_UTR	Exon 1 of 8	ENSP00000603658.1

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

GnomAD2 exomes AF: 0.00753 AC: 931 AN: 123674 AF XY: 0.00737

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 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

African (AFR) AF: 0.00146 AC: 40 AN: 27334

American (AMR) AF: 0.00404 AC: 135 AN: 33382

Ashkenazi Jewish (ASJ) AF: 0.0143 AC: 342 AN: 23932

East Asian (EAS) AF: 0.00 AC: 0 AN: 31288

South Asian (SAS) AF: 0.000536 AC: 41 AN: 76428

European-Finnish (FIN) AF: 0.00735 AC: 348 AN: 47372

Middle Eastern (MID) AF: 0.00144 AC: 8 AN: 5542

European-Non Finnish (NFE) AF: 0.0101 AC: 10694 AN: 1057634

Other (OTH) AF: 0.00809 AC: 454 AN: 56138

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

African (AFR) AF: 0.00166 AC: 69 AN: 41508

American (AMR) AF: 0.00674 AC: 103 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00694 AC: 73 AN: 10514

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

European-Non Finnish (NFE) AF: 0.0101 AC: 683 AN: 67894

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.00299 Hom.: 0

Bravo AF: 0.00651

ClinVar

ClinVar submissions

Significance: Likely benign

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
PhyloP100		0.36
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: COSV59796776; COSMIC: COSV59796776;