rs2872817

Positions:

• chrX-154330068-A-G

Variant summary

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

The NM_012253.4(TKTL1):​c.*380A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 128,469 control chromosomes in the GnomAD database, including 2,732 homozygotes. There are 8,861 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 0.24 (2389 hom., 7994 hem., cov: 23)
  • Exomes 𝑓: 0.22 (343 hom. 867 hem.)
• Consequence: TKTL1 NM_012253.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TKTL1	NM_012253.4	c.*380A>G		3_prime_UTR_variant	13/13	ENST00000369915.8
TKTL1	NM_001145933.2	c.*380A>G		3_prime_UTR_variant	13/13
TKTL1	NM_001145934.2	c.*380A>G		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TKTL1	ENST00000369915.8	c.*380A>G		3_prime_UTR_variant	13/13	1	NM_012253.4	P1
TKTL1	ENST00000369912.2	c.*380A>G		3_prime_UTR_variant	12/12	1
TKTL1	ENST00000710264.1	c.*691A>G		3_prime_UTR_variant, NMD_transcript_variant	13/13

Frequencies

GnomAD3 genomes AF: 0.236 AC: 26335 AN: 111502 Hom.: 2387 Cov.: 23 AF XY: 0.237 AC XY: 7980 AN XY: 33738

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.00873

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.221 AC: 3734 AN: 16910 Hom.: 343 Cov.: 0 AF XY: 0.295 AC XY: 867 AN XY: 2936

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.236 AC: 26358 AN: 111559 Hom.: 2389 Cov.: 23 AF XY: 0.236 AC XY: 7994 AN XY: 33805

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.257

Alfa AF: 0.212 Hom.: 6206

Bravo AF: 0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.048
DANN	Benign	0.21

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: rs2872817; hg19: chrX-153558418;