11-764414-A-G

Variant names:

• chr11-764414-A-G
• rs11302
• NM_006755.2:c.962A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006755.2(TALDO1):​c.962A>G​(p.Lys321Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00564 in 1,611,302 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (19 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (54 hom.)
• Consequence: TALDO1 NM_006755.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 6.61
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015927285).
• BP6: Variant 11-764414-A-G is Benign according to our data. Variant chr11-764414-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 306139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1643/149452) while in subpopulation AFR AF = 0.028 (1160/41384). AF 95% confidence interval is 0.0267. There are 19 homozygotes in GnomAd4. There are 769 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TALDO1	NM_006755.2	c.962A>G	p.Lys321Arg	missense_variant	Exon 7 of 8	ENST00000319006.8	NP_006746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TALDO1	ENST00000319006.8	c.962A>G	p.Lys321Arg	missense_variant	Exon 7 of 8	1	NM_006755.2	ENSP00000321259.3
TALDO1	ENST00000528097.5	c.*1A>G		3_prime_UTR_variant	Exon 7 of 8	1		ENSP00000437098.1
TALDO1	ENST00000530666.1	n.433A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
TALDO1	ENST00000532202.1	n.45A>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1641 AN: 149332 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00343

Gnomad ASJ AF: 0.0370

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.000865

Gnomad MID AF: 0.0197

Gnomad NFE AF: 0.00399

Gnomad OTH AF: 0.00988

GnomAD2 exomes AF: 0.00550 AC: 1380 AN: 251106 AF XY: 0.00479

Gnomad AFR exome AF: 0.0283

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.0347

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.00366

Gnomad OTH exome AF: 0.00523

GnomAD4 exome AF: 0.00509 AC: 7444 AN: 1461850 Hom.: 54 Cov.: 32 AF XY: 0.00490 AC XY: 3563 AN XY: 727226

African (AFR) AF: 0.0294 AC: 983 AN: 33480

American (AMR) AF: 0.00257 AC: 115 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0327 AC: 854 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00118 AC: 102 AN: 86256

European-Finnish (FIN) AF: 0.000468 AC: 25 AN: 53416

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.00436 AC: 4844 AN: 1111984

Other (OTH) AF: 0.00811 AC: 490 AN: 60392

GnomAD4 genome AF: 0.0110 AC: 1643 AN: 149452 Hom.: 19 Cov.: 33 AF XY: 0.0105 AC XY: 769 AN XY: 73066

African (AFR) AF: 0.0280 AC: 1160 AN: 41384

American (AMR) AF: 0.00342 AC: 51 AN: 14900

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 126 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4796

European-Finnish (FIN) AF: 0.000865 AC: 9 AN: 10400

Middle Eastern (MID) AF: 0.0211 AC: 6 AN: 284

European-Non Finnish (NFE) AF: 0.00399 AC: 264 AN: 66146

Other (OTH) AF: 0.00978 AC: 20 AN: 2046

Alfa AF: 0.00692 Hom.: 15

Bravo AF: 0.0118

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00389 AC: 15

ESP6500AA AF: 0.0313 AC: 138

ESP6500EA AF: 0.00651 AC: 56

ExAC AF: 0.00545 AC: 662

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00496

EpiControl AF: 0.00510

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 11, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Deficiency of transaldolase Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.016	T
MetaSVM	Uncertain	-0.040	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.4	N
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.037	D
Polyphen		0.69	P
Vest4		0.54
MVP		0.94
MPC		0.30
ClinPred		0.041	T
GERP RS		4.1
Varity_R		0.49
gMVP		0.64
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11302; hg19: chr11-764414; COSMIC: COSV59797634; COSMIC: COSV59797634;