chr11-763998-G-C

Variant names:

• chr11-763998-G-C
• rs3891028
• NM_006755.2:c.835+54G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006755.2(TALDO1):​c.835+54G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,579,332 control chromosomes in the GnomAD database, including 44,701 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 0.28 (7411 hom., cov: 33)
  • Exomes 𝑓: 0.22 (37290 hom.)
• Consequence: TALDO1 NM_006755.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 4 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, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TALDO1	NM_006755.2	c.835+54G>C		intron_variant	Intron 6 of 7	ENST00000319006.8	NP_006746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TALDO1	ENST00000319006.8	c.835+54G>C		intron_variant	Intron 6 of 7	1	NM_006755.2	ENSP00000321259.3
TALDO1	ENST00000528097.5	c.831+58G>C		intron_variant	Intron 6 of 7	1		ENSP00000437098.1
TALDO1	ENST00000530666.1	n.17G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
TALDO1	ENST00000530440.1	n.*548G>C		downstream_gene_variant		3		ENSP00000433501.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43075 AN: 152086 Hom.: 7402 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0977

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.221 AC: 315582 AN: 1427128 Hom.: 37290 Cov.: 31 AF XY: 0.218 AC XY: 154378 AN XY: 709514

African (AFR) AF: 0.494 AC: 16289 AN: 33000

American (AMR) AF: 0.149 AC: 6425 AN: 43012

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2992 AN: 24970

East Asian (EAS) AF: 0.0958 AC: 3767 AN: 39304

South Asian (SAS) AF: 0.138 AC: 11578 AN: 83770

European-Finnish (FIN) AF: 0.228 AC: 9494 AN: 41680

Middle Eastern (MID) AF: 0.129 AC: 543 AN: 4212

European-Non Finnish (NFE) AF: 0.229 AC: 251545 AN: 1097964

Other (OTH) AF: 0.219 AC: 12949 AN: 59216

GnomAD4 genome AF: 0.283 AC: 43109 AN: 152204 Hom.: 7411 Cov.: 33 AF XY: 0.278 AC XY: 20660 AN XY: 74430

African (AFR) AF: 0.487 AC: 20208 AN: 41532

American (AMR) AF: 0.197 AC: 3017 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3470

East Asian (EAS) AF: 0.0979 AC: 507 AN: 5178

South Asian (SAS) AF: 0.139 AC: 670 AN: 4828

European-Finnish (FIN) AF: 0.217 AC: 2297 AN: 10608

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15340 AN: 67978

Other (OTH) AF: 0.253 AC: 534 AN: 2114

Alfa AF: 0.130 Hom.: 228

Bravo AF: 0.289

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	0.47
PhyloP100		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs3891028; hg19: chr11-763998;