dbSNP rs1132543: TK1:p.Val106Met (chr17-78175606-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003258.5(TK1):c.316G>A(p.Val106Met) variant causes a missense change. The variant allele was found at a frequency of 0.00183 in 1,613,464 control chromosomes in the GnomAD database, including 6 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 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 6 hom. )

Consequence

TK1
NM_003258.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.09

Publications

13 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04470408).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TK1	NM_003258.5 link	c.316G>A	p.Val106Met	missense_variant	Exon 5 of 7	ENST00000301634.12	NP_003249.3	P04183A0A384MDV9
TK1	NM_001363848.1 link	c.316G>A	p.Val106Met	missense_variant	Exon 5 of 6		NP_001350777.1
TK1	NM_001346663.2 link	c.316G>A	p.Val106Met	missense_variant	Exon 5 of 7		NP_001333592.1	K7ES52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TK1	ENST00000301634.12 link	c.316G>A	p.Val106Met	missense_variant	Exon 5 of 7	1	NM_003258.5	ENSP00000301634.6		P04183

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

165

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00123

AC:

308

AN:

249786

AF XY:

0.00125

show subpopulations

Gnomad AFR exome

AF:

0.000926

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000469

Gnomad NFE exome

AF:

0.00210

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00191

AC:

2792

AN:

1461158

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

1353

AN XY:

726832

show subpopulations

African (AFR)

AF:

0.000807

AC:

AN:

33478

American (AMR)

AF:

0.00114

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.0000754

AC:

AN:

53064

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00234

AC:

2597

AN:

1111754

Other (OTH)

AF:

0.00174

AC:

105

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

141

282

424

565

706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00108

AC:

165

AN:

152306

Hom.:

Cov.:

AF XY:

0.000859

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41582

American (AMR)

AF:

0.000523

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00193

AC:

131

AN:

68026

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00110

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00114

AC:

139

EpiCase

AF:

0.00147

EpiControl

AF:

0.00213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.80

D;.;.;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

T;D;T;D

M_CAP

Benign

0.064

MetaRNN

Benign

0.045

T;T;T;T

MetaSVM

Uncertain

0.073

MutationAssessor

Pathogenic

3.4

M;.;.;.

PhyloP100

4.1

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.8

D;.;.;.

REVEL

Uncertain

0.58

Sift

Uncertain

0.016

D;.;.;.

Sift4G

Uncertain

0.015

D;D;D;.

Polyphen

0.99

D;.;.;.

Vest4

0.38

MVP

0.47

MPC

1.3

ClinPred

0.12

GERP RS

4.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.48

gMVP

0.77

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over