chr11-747445-TCGC-T

Variant names:

• chr11-747445-TCGC-T
• rs71464113
• ENST00000528097.5:c.-21_-19delCGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000528097.5(TALDO1):​c.-21_-19delCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000756 in 1,493,514 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00084 (0 hom.)
• Consequence: TALDO1 ENST00000528097.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• 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: Uncertain_significance. The variant received 0 ACMG points.

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_-34delCGC		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.-21_-19delCGC		5_prime_UTR	Exon 1 of 8	ENSP00000437098.1	F2Z393
	TALDO1	ENST00000896396.1		c.-21_-19delCGC		5_prime_UTR	Exon 1 of 9	ENSP00000566455.1
	TALDO1	ENST00000933599.1		c.-21_-19delCGC		5_prime_UTR	Exon 1 of 8	ENSP00000603658.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151838 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00296 AC: 366 AN: 123674 AF XY: 0.00280

Gnomad AFR exome AF: 0.00388

Gnomad AMR exome AF: 0.00385

Gnomad ASJ exome AF: 0.000560

Gnomad EAS exome AF: 0.00583

Gnomad FIN exome AF: 0.00299

Gnomad NFE exome AF: 0.00298

Gnomad OTH exome AF: 0.00282

GnomAD4 exome AF: 0.000840 AC: 1127 AN: 1341570 Hom.: 0 AF XY: 0.000828 AC XY: 550 AN XY: 664040

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000965 AC: 26 AN: 26952

American (AMR) AF: 0.00264 AC: 86 AN: 32600

Ashkenazi Jewish (ASJ) AF: 0.000679 AC: 16 AN: 23564

East Asian (EAS) AF: 0.00159 AC: 49 AN: 30816

South Asian (SAS) AF: 0.00109 AC: 81 AN: 74556

European-Finnish (FIN) AF: 0.00133 AC: 62 AN: 46466

Middle Eastern (MID) AF: 0.000183 AC: 1 AN: 5476

European-Non Finnish (NFE) AF: 0.000732 AC: 766 AN: 1045846

Other (OTH) AF: 0.000723 AC: 40 AN: 55294

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151944 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74278

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41506

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67890

Other (OTH) AF: 0.00 AC: 0 AN: 2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00334 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.15
Mutation Taster		=299/1	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: rs71464113; hg19: chr11-747445; COSMIC: COSV100032921; COSMIC: COSV100032921;