X-154295882-C-T

Position:

chrX-154295882-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012253.4(TKTL1):c.23C>T(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,210,099 control chromosomes in the GnomAD database, including 8 homozygotes. There are 300 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 5 hom., 140 hem., cov: 23)

Exomes 𝑓: 0.00055 ( 3 hom. 160 hem. )

Consequence

TKTL1
NM_012253.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.845

Variant links:

Genes affected

TKTL1 (HGNC:11835): (transketolase like 1) The protein encoded by this gene is a transketolase that acts as a homodimer and catalyzes the conversion of sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to D-ribose 5-phosphate and D-xylulose 5-phosphate. This reaction links the pentose phosphate pathway with the glycolytic pathway. Variations in this gene may be the cause of Wernicke-Korsakoff syndrome. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

TKTL1 links:

TEX28 (HGNC:2563): (testis expressed 28) Predicted to be integral component of membrane. Predicted to be active in endomembrane system. [provided by Alliance of Genome Resources, Apr 2022]

TEX28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037414134).

BP6

Variant X-154295882-C-T is Benign according to our data. Variant chrX-154295882-C-T is described in ClinVar as [Benign]. Clinvar id is 779002.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00055 (604/1097960) while in subpopulation AFR AF= 0.018 (474/26395). AF 95% confidence interval is 0.0166. There are 3 homozygotes in gnomad4_exome. There are 160 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TKTL1	NM_012253.4 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/13	ENST00000369915.8	NP_036385.3
TKTL1	NM_001145933.2 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/13		NP_001139405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TKTL1	ENST00000369915.8 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/13	1	NM_012253.4	ENSP00000358931	P1	P51854-3
TKTL1	ENST00000710264.1 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant, NMD_transcript_variant	1/13			ENSP00000518160
TKTL1	ENST00000439635.5 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant, NMD_transcript_variant	1/5	4		ENSP00000399763
TEX28	ENST00000617213.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00437

AC:

490

AN:

112083

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

133

AN XY:

34261

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

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:

0.0000377

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.00139

AC:

254

AN:

182831

Hom.:

AF XY:

0.000832

AC XY:

AN XY:

67347

show subpopulations

Gnomad AFR exome

AF:

0.0172

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000368

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000550

AC:

604

AN:

1097960

Hom.:

Cov.:

AF XY:

0.000440

AC XY:

160

AN XY:

363324

show subpopulations

Gnomad4 AFR exome

AF:

0.0180

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000321

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00443

AC:

497

AN:

112139

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

140

AN XY:

34327

show subpopulations

Gnomad4 AFR

AF:

0.0149

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000377

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.00571

ESP6500AA

AF:

0.0154

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00139

AC:

169

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 30, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.14

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.22

REVEL

Benign

0.0

Sift

Benign

0.29

Sift4G

Benign

0.13

Polyphen

0.0010

Vest4

0.078

MVP

0.18

MPC

0.057

ClinPred

0.0086

GERP RS

-2.9

Varity_R

0.036

gMVP

0.10

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

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