NM_006755.2:c.68C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_006755.2(TALDO1):c.68C>G(p.Thr23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000432 in 1,593,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

TALDO1
NM_006755.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 2.52

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

transaldolase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

TALDO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15134662).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000459 (70/152348) while in subpopulation AMR AF = 0.00144 (22/15310). AF 95% confidence interval is 0.000972. There are 0 homozygotes in GnomAd4. There are 32 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006755.2. 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.68C>G	p.Thr23Ser	missense	Exon 1 of 8	NP_006746.1	A0A140VK56

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TALDO1	ENST00000319006.8	TSL:1 MANE Select	c.68C>G	p.Thr23Ser	missense	Exon 1 of 8	ENSP00000321259.3	P37837-1
TALDO1	ENST00000528097.5	TSL:1	c.68C>G	p.Thr23Ser	missense	Exon 1 of 8	ENSP00000437098.1	F2Z393
TALDO1	ENST00000896396.1		c.68C>G	p.Thr23Ser	missense	Exon 1 of 9	ENSP00000566455.1

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

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:

0.000588

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000248

AC:

AN:

218004

AF XY:

0.000234

show subpopulations

Gnomad AFR exome

AF:

0.0000879

Gnomad AMR exome

AF:

0.000345

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000406

Gnomad OTH exome

AF:

0.000375

GnomAD4 exome

AF:

0.000429

AC:

619

AN:

1441580

Hom.:

Cov.:

AF XY:

0.000409

AC XY:

293

AN XY:

716572

show subpopulations

African (AFR)

AF:

0.000128

AC:

AN:

31282

American (AMR)

AF:

0.000464

AC:

AN:

43136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25634

East Asian (EAS)

AF:

0.00

AC:

AN:

37788

South Asian (SAS)

AF:

0.00

AC:

AN:

83132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.000522

AC:

577

AN:

1104372

Other (OTH)

AF:

0.000303

AC:

AN:

59482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000459

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41586

American (AMR)

AF:

0.00144

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68030

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000447

Hom.:

Bravo

AF:

0.000676

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000350

AC:

ExAC

AF:

0.000200

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3468

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of transaldolase (1)

Inborn genetic diseases (1)

not provided (1)

TALDO1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.77

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.5

PhyloP100

2.5

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.33

Sift

Benign

0.036

Sift4G

Uncertain

0.043

Polyphen

0.0030

Vest4

0.12

MutPred

0.54

Gain of sheet (P = 0.0477)

MVP

0.86

MPC

0.064

ClinPred

0.052

GERP RS

1.9

PromoterAI

-0.081

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.33

gMVP

0.36

Mutation Taster

=85/15

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over