Variant chrX-154320815-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2

The ENST00000369915.8(TKTL1):c.1088T>G(p.Phe363Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,097,820 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000024 ( 0 hom. 10 hem. )

Consequence

TKTL1
ENST00000369915.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.74

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:

TKTL1 (HGNC:):

TKTL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.987

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TKTL1	NM_012253.4 linkuse as main transcript	c.1088T>G	p.Phe363Cys	missense_variant	8/13	ENST00000369915.8	NP_036385.3	P51854-3
TKTL1	NM_001145933.2 linkuse as main transcript	c.1070T>G	p.Phe357Cys	missense_variant	8/13		NP_001139405.1	B7Z7I0
TKTL1	NM_001145934.2 linkuse as main transcript	c.920T>G	p.Phe307Cys	missense_variant	7/12		NP_001139406.1	P51854-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TKTL1	ENST00000369915.8 linkuse as main transcript	c.1088T>G	p.Phe363Cys	missense_variant	8/13	1	NM_012253.4	ENSP00000358931.3	P51854-3
TKTL1	ENST00000369912.2 linkuse as main transcript	c.920T>G	p.Phe307Cys	missense_variant	7/12	1		ENSP00000358928.2	P51854-4
TKTL1	ENST00000465168.1 linkuse as main transcript	n.279T>G		non_coding_transcript_exon_variant	2/4	4
TKTL1	ENST00000710264.1 linkuse as main transcript	n.1088T>G		non_coding_transcript_exon_variant	8/13			ENSP00000518160.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183500

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67928

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000237

AC:

AN:

1097820

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

363180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 03, 2022

The c.1088T>G (p.F363C) alteration is located in exon 8 (coding exon 8) of the TKTL1 gene. This alteration results from a T to G substitution at nucleotide position 1088, causing the phenylalanine (F) at amino acid position 363 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Pathogenic

0.64

BayesDel_noAF

Pathogenic

0.73

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.92

D;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.99

D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

4.5

H;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-7.4

D;D

REVEL

Pathogenic

0.96

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.87

MutPred

0.91

Gain of catalytic residue at F363 (P = 0.0366);.;

MVP

0.99

MPC

0.43

ClinPred

1.0

GERP RS

4.8

Varity_R

0.91

gMVP

0.73

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