11-764414-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.61

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 306139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-764414-A-G is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

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 link	c.962A>G	p.Lys321Arg	missense_variant	Exon 7 of 8	ENST00000319006.8	NP_006746.1	P37837-1A0A140VK56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TALDO1	ENST00000319006.8 link	c.962A>G	p.Lys321Arg	missense_variant	Exon 7 of 8	1	NM_006755.2	ENSP00000321259.3	P37837-1
TALDO1	ENST00000528097.5 link	c.*1A>G		3_prime_UTR_variant	Exon 7 of 8	1		ENSP00000437098.1	F2Z393
TALDO1	ENST00000530666.1 link	n.433A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
TALDO1	ENST00000532202.1 link	n.45A>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1641

AN:

149332

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00550

AC:

1380

AN:

251106

Hom.:

AF XY:

0.00479

AC XY:

651

AN XY:

135810

show subpopulations

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 SAS exome

AF:

0.000980

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.:

Cov.:

AF XY:

0.00490

AC XY:

3563

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0294

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.0327

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.00436

Gnomad4 OTH exome

AF:

0.00811

GnomAD4 genome

AF:

0.0110

AC:

1643

AN:

149452

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

769

AN XY:

73066

show subpopulations

Gnomad4 AFR

AF:

0.0280

Gnomad4 AMR

AF:

0.00342

Gnomad4 ASJ

AF:

0.0370

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.000865

Gnomad4 NFE

AF:

0.00399

Gnomad4 OTH

AF:

0.00978

Alfa

AF:

0.00657

Hom.:

Bravo

AF:

0.0118

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.0313

AC:

138

ESP6500EA

AF:

0.00651

AC:

ExAC

AF:

0.00545

AC:

662

Asia WGS

AF:

0.00404

AC:

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

LINK: link

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

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.016

MetaSVM

Uncertain

-0.040

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.4

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.037

Polyphen

0.69

Vest4

0.54

MVP

0.94

MPC

0.30

ClinPred

0.041

GERP RS

4.1

Varity_R

0.49

gMVP

0.64

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over