Variant rs375708499 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003258.5(TK1):c.245G>T(p.Arg82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TK1
NM_003258.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.399

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15495458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TK1	NM_003258.5 link	c.245G>T	p.Arg82Leu	missense_variant	Exon 4 of 7	ENST00000301634.12	NP_003249.3	P04183A0A384MDV9
TK1	NM_001363848.1 link	c.245G>T	p.Arg82Leu	missense_variant	Exon 4 of 6		NP_001350777.1
TK1	NM_001346663.2 link	c.245G>T	p.Arg82Leu	missense_variant	Exon 4 of 7		NP_001333592.1	K7ES52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TK1	ENST00000301634.12 link	c.245G>T	p.Arg82Leu	missense_variant	Exon 4 of 7	1	NM_003258.5	ENSP00000301634.6		P04183

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000448

AC:

AN:

223166

Hom.:

AF XY:

0.00

AC XY:

AN XY:

120960

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000593

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716782

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000204

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.46

T;.;.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.0040

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;.;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.8

N;.;.;.

REVEL

Benign

0.091

Sift

Benign

0.55

T;.;.;.

Sift4G

Benign

0.34

T;T;T;.

Polyphen

0.0

B;.;.;.

Vest4

0.55

MutPred

0.40

Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);.;

MVP

0.49

MPC

0.57

ClinPred

0.35

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.66

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