X-154326058-C-G

Variant names:

• chrX-154326058-C-G
• rs766420
• NM_012253.4:c.1401+636C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012253.4(TKTL1):​c.1401+636C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 111,255 control chromosomes in the GnomAD database, including 5,031 homozygotes. There are 10,432 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (5031 hom., 10432 hem., cov: 23)
• Consequence: TKTL1 NM_012253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TKTL1	NM_012253.4	c.1401+636C>G		intron_variant	Intron 10 of 12	ENST00000369915.8	NP_036385.3
TKTL1	NM_001145933.2	c.1383+636C>G		intron_variant	Intron 10 of 12		NP_001139405.1
TKTL1	NM_001145934.2	c.1233+636C>G		intron_variant	Intron 9 of 11		NP_001139406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TKTL1	ENST00000369915.8	c.1401+636C>G		intron_variant	Intron 10 of 12	1	NM_012253.4	ENSP00000358931.3
TKTL1	ENST00000369912.2	c.1233+636C>G		intron_variant	Intron 9 of 11	1		ENSP00000358928.2
TKTL1	ENST00000710264.1	n.1401+636C>G		intron_variant	Intron 10 of 12			ENSP00000518160.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 34930 AN: 111199 Hom.: 5027 Cov.: 23 AF XY: 0.311 AC XY: 10403 AN XY: 33433

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.314 AC: 34967 AN: 111255 Hom.: 5031 Cov.: 23 AF XY: 0.311 AC XY: 10432 AN XY: 33499

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.311

Alfa AF: 0.194 Hom.: 4500

Bravo AF: 0.324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs766420; hg19: chrX-153554404;