Variant 17-78182670-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_003258.5(TK1):c.222G>A(p.Glu74Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 1,579,492 control chromosomes in the GnomAD database, including 2,570 homozygotes. 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 0.034 ( 252 hom., cov: 32)

Exomes 𝑓: 0.034 ( 2318 hom. )

Consequence

TK1
NM_003258.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.337

Variant links:

Genes affected

TK1 (HGNC:11830): (thymidine kinase 1) The protein encoded by this gene is a cytosolic enzyme that catalyzes the addition of a gamma-phosphate group to thymidine. This creates dTMP and is the first step in the biosynthesis of dTTP, which is one component required for DNA replication. The encoded protein, whose levels fluctuate depending on the cell cycle stage, can act as a low activity dimer or a high activity tetramer. High levels of this protein have been used as a biomarker for diagnosing and categorizing many types of cancers. [provided by RefSeq, Oct 2016]

TK1 links:

TK1 (HGNC:):

TK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP7

Synonymous conserved (PhyloP=-0.337 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TK1	NM_003258.5 linkuse as main transcript	c.222G>A	p.Glu74Glu	synonymous_variant	4/7	ENST00000301634.12	NP_003249.3	P04183A0A384MDV9
TK1	NM_001363848.1 linkuse as main transcript	c.222G>A	p.Glu74Glu	synonymous_variant	4/6		NP_001350777.1
TK1	NM_001346663.2 linkuse as main transcript	c.222G>A	p.Glu74Glu	synonymous_variant	4/7		NP_001333592.1	K7ES52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TK1	ENST00000301634.12 linkuse as main transcript	c.222G>A	p.Glu74Glu	synonymous_variant	4/7	1	NM_003258.5	ENSP00000301634.6		P04183

Frequencies

GnomAD3 genomes

AF:

0.0342

AC:

5198

AN:

152112

Hom.:

252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0508

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0278

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0234

Gnomad OTH

AF:

0.0335

GnomAD3 exomes

AF:

0.0589

AC:

12024

AN:

204050

Hom.:

764

AF XY:

0.0604

AC XY:

6678

AN XY:

110638

show subpopulations

Gnomad AFR exome

AF:

0.0160

Gnomad AMR exome

AF:

0.0781

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.239

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.0257

Gnomad NFE exome

AF:

0.0246

Gnomad OTH exome

AF:

0.0459

GnomAD4 exome

AF:

0.0341

AC:

48672

AN:

1427262

Hom.:

2318

Cov.:

AF XY:

0.0365

AC XY:

25815

AN XY:

707940

show subpopulations

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.0784

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.0246

Gnomad4 NFE exome

AF:

0.0202

Gnomad4 OTH exome

AF:

0.0411

GnomAD4 genome

AF:

0.0342

AC:

5201

AN:

152230

Hom.:

252

Cov.:

AF XY:

0.0369

AC XY:

2747

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0167

Gnomad4 AMR

AF:

0.0506

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.0278

Gnomad4 NFE

AF:

0.0234

Gnomad4 OTH

AF:

0.0345

Alfa

AF:

0.0281

Hom.:

Bravo

AF:

0.0363

Asia WGS

AF:

0.154

AC:

534

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

4.7

DANN

Benign

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over