3-53225846-T-C

Position:

• chr3-53225846-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_001064.4(TKT):​c.1782A>G​(p.Arg594Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000704 in 1,614,038 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (1 hom.)
• Consequence: TKT NM_001064.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.07

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]

TKT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 3-53225846-T-C is Benign according to our data. Variant chr3-53225846-T-C is described in ClinVar as [Benign]. Clinvar id is 720422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TKT	NM_001064.4	c.1782A>G	p.Arg594Arg	synonymous_variant	14/14	ENST00000462138.6	NP_001055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TKT	ENST00000462138.6	c.1782A>G	p.Arg594Arg	synonymous_variant	14/14	1	NM_001064.4	ENSP00000417773.1

Frequencies

GnomAD3 genomes AF: 0.00178 AC: 270 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00432

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.000963 AC: 242 AN: 251388 Hom.: 1 AF XY: 0.000868 AC XY: 118 AN XY: 135880

Gnomad AFR exome AF: 0.00338

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.00456

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.000593 AC: 867 AN: 1461842 Hom.: 1 Cov.: 32 AF XY: 0.000582 AC XY: 423 AN XY: 727222

Gnomad4 AFR exome AF: 0.00418

Gnomad4 AMR exome AF: 0.00188

Gnomad4 ASJ exome AF: 0.00539

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000431

Gnomad4 NFE exome AF: 0.000335

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.00177 AC: 270 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.00183 AC XY: 136 AN XY: 74404

Gnomad4 AFR AF: 0.00431

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00139 Hom.: 0

Bravo AF: 0.00215

EpiCase AF: 0.000327

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.7
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs146102577; hg19: chr3-53259862;