X-154326058-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012253.4. 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
	TKTL1	NM_012253.4	MANE Select	c.1401+636C>G		intron	N/A	NP_036385.3
	TKTL1	NM_001145933.2		c.1383+636C>G		intron	N/A	NP_001139405.1
	TKTL1	NM_001145934.2		c.1233+636C>G		intron	N/A	NP_001139406.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TKTL1	ENST00000369915.8	TSL:1 MANE Select	c.1401+636C>G		intron	N/A	ENSP00000358931.3
	TKTL1	ENST00000369912.2	TSL:1	c.1233+636C>G		intron	N/A	ENSP00000358928.2
	TKTL1	ENST00000710264.1		n.1401+636C>G		intron	N/A	ENSP00000518160.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 34930 AN: 111199 Hom.: 5027 Cov.: 23

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

African (AFR) AF: 0.566 AC: 17251 AN: 30489

American (AMR) AF: 0.246 AC: 2593 AN: 10530

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 567 AN: 2633

East Asian (EAS) AF: 0.238 AC: 841 AN: 3533

South Asian (SAS) AF: 0.533 AC: 1437 AN: 2695

European-Finnish (FIN) AF: 0.195 AC: 1172 AN: 6001

Middle Eastern (MID) AF: 0.298 AC: 64 AN: 215

European-Non Finnish (NFE) AF: 0.198 AC: 10472 AN: 52976

Other (OTH) AF: 0.311 AC: 468 AN: 1507

Alfa AF: 0.194 Hom.: 4500

Bravo AF: 0.324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.69
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs766420; hg19: chrX-153554404;