rs1132543

Positions:

• chr17-78175606-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TK1	NM_003258.5	c.316G>A	p.Val106Met	missense_variant	5/7	ENST00000301634.12
TK1	NM_001363848.1	c.316G>A	p.Val106Met	missense_variant	5/6
TK1	NM_001346663.2	c.316G>A	p.Val106Met	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TK1	ENST00000301634.12	c.316G>A	p.Val106Met	missense_variant	5/7	1	NM_003258.5	P1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 165 AN: 152188 Hom.: 0 Cov.: 32

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

GnomAD3 exomes AF: 0.00123 AC: 308 AN: 249786 Hom.: 1 AF XY: 0.00125 AC XY: 169 AN XY: 135018

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 SAS exome AF: 0.0000981

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.: 6 Cov.: 31 AF XY: 0.00186 AC XY: 1353 AN XY: 726832

Gnomad4 AFR exome AF: 0.000807

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000754

Gnomad4 NFE exome AF: 0.00234

Gnomad4 OTH exome AF: 0.00174

GnomAD4 genome AF: 0.00108 AC: 165 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.000859 AC XY: 64 AN XY: 74462

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00177 Hom.: 1

Bravo AF: 0.00110

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00140 AC: 12

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	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	D;.;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T;D;T;D
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.045	T;T;T;T
MetaSVM	Uncertain	0.073	D
MutationAssessor	Pathogenic	3.4	M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.64	T
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	T
GERP RS		4.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.48
gMVP		0.77

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: rs1132543; hg19: chr17-76171687;