rs775606662

Variant names:

• chr17-78182674-A-C
• rs775606662
• NM_003258.5:c.218T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-78182674-A-C
• chr17-78182674-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003258.5(TK1):​c.218T>G​(p.Met73Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,120 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TK1 NM_003258.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.44

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TK1	NM_003258.5	c.218T>G	p.Met73Arg	missense_variant	Exon 4 of 7	ENST00000301634.12	NP_003249.3
TK1	NM_001363848.1	c.218T>G	p.Met73Arg	missense_variant	Exon 4 of 6		NP_001350777.1
TK1	NM_001346663.2	c.218T>G	p.Met73Arg	missense_variant	Exon 4 of 7		NP_001333592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TK1	ENST00000301634.12	c.218T>G	p.Met73Arg	missense_variant	Exon 4 of 7	1	NM_003258.5	ENSP00000301634.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.74	D;.;.;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.0079	T
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.8	L;.;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.6	D;.;.;.
REVEL	Uncertain	0.44
Sift	Benign	0.053	T;.;.;.
Sift4G	Benign	0.18	T;T;T;.
Polyphen		0.14	B;.;.;.
Vest4		0.96
MutPred		0.51		Gain of disorder (P = 0.0521);Gain of disorder (P = 0.0521);Gain of disorder (P = 0.0521);.;
MVP		0.68
MPC		0.71
ClinPred		0.94	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.97

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: rs775606662; hg19: chr17-76178755;