3-53225980-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001064.4(TKT):c.1697-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,558,256 control chromosomes in the GnomAD database, including 143,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11880 hom., cov: 32)
  • Exomes 𝑓: 0.43 (132001 hom.)
• Consequence: TKT NM_001064.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.119

Genes affected

TKT (HGNC:11834): (transketolase) This gene encodes a thiamine-dependent enzyme which plays a role in the channeling of excess sugar phosphates to glycolysis in the pentose phosphate pathway. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-53225980-G-A is Benign according to our data. Variant chr3-53225980-G-A is described in ClinVar as [Benign]. Clinvar id is 1342213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TKT	NM_001064.4	c.1697-49C>T		intron_variant		ENST00000462138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TKT	ENST00000462138.6	c.1697-49C>T		intron_variant		1	NM_001064.4	P3

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58065 AN: 152020 Hom.: 11866 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.432

GnomAD3 exomes AF: 0.442 AC: 96863 AN: 219080 Hom.: 21988 AF XY: 0.450 AC XY: 53192 AN XY: 118112

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.525

Gnomad EAS exome AF: 0.600

Gnomad SAS exome AF: 0.547

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.438

Gnomad OTH exome AF: 0.464

GnomAD4 exome AF: 0.430 AC: 604622 AN: 1406114 Hom.: 132001 Cov.: 26 AF XY: 0.434 AC XY: 302067 AN XY: 695240

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.410

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.560

Gnomad4 SAS exome AF: 0.537

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.382 AC: 58107 AN: 152142 Hom.: 11880 Cov.: 32 AF XY: 0.386 AC XY: 28683 AN XY: 74376

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.431

Alfa AF: 0.425 Hom.: 20277

Bravo AF: 0.377

Asia WGS AF: 0.525 AC: 1826 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Transketolase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.9
Dann	Benign	0.58

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: rs3816767; hg19: chr3-53259996; COSMIC: COSV56247405; COSMIC: COSV56247405;