11-762441-A-C

Position:

• chr11-762441-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006755.2(TALDO1):​c.462-903A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 150,222 control chromosomes in the GnomAD database, including 13,408 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13408 hom., cov: 34)
• Consequence: TALDO1 NM_006755.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TALDO1	NM_006755.2	c.462-903A>C		intron_variant		ENST00000319006.8	NP_006746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TALDO1	ENST00000319006.8	c.462-903A>C		intron_variant		1	NM_006755.2	ENSP00000321259	P1
TALDO1	ENST00000528097.5	c.462-903A>C		intron_variant		1		ENSP00000437098
TALDO1	ENST00000528070.5	c.*460-903A>C		intron_variant, NMD_transcript_variant		5		ENSP00000435042
TALDO1	ENST00000530440.1	c.*121-903A>C		intron_variant, NMD_transcript_variant		3		ENSP00000433501

Frequencies

GnomAD3 genomes AF: 0.405 AC: 60756 AN: 150104 Hom.: 13395 Cov.: 34

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.405 AC: 60792 AN: 150222 Hom.: 13408 Cov.: 34 AF XY: 0.403 AC XY: 29596 AN XY: 73468

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.400

Alfa AF: 0.432 Hom.: 1449

Bravo AF: 0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs4963163; hg19: chr11-762441;