rs766420

Positions:

• chrX-154326058-C-A
• chrX-154326058-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012253.4(TKTL1):​c.1401+636C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000899 in 111,238 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.0000090 (0 hom., 1 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TKTL1	NM_012253.4	c.1401+636C>A		intron_variant		ENST00000369915.8
TKTL1	NM_001145933.2	c.1383+636C>A		intron_variant
TKTL1	NM_001145934.2	c.1233+636C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TKTL1	ENST00000369915.8	c.1401+636C>A		intron_variant		1	NM_012253.4	P1
TKTL1	ENST00000369912.2	c.1233+636C>A		intron_variant		1
TKTL1	ENST00000710264.1	c.1401+636C>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00000899 AC: 1 AN: 111238 Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1 AN XY: 33448

Gnomad AFR AF: 0.0000329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000899 AC: 1 AN: 111238 Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1 AN XY: 33448

Gnomad4 AFR AF: 0.0000329

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.64

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;