chr17-78175606-C-T

Variant names:

• chr17-78175606-C-T
• rs1132543
• NM_003258.5:c.316G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001363848.1(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_001363848.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09
• Publications: 13 publications found

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363848.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TK1	NM_003258.5	MANE Select	c.316G>A	p.Val106Met	missense	Exon 5 of 7	NP_003249.3
	TK1	NM_001363848.1		c.316G>A	p.Val106Met	missense	Exon 5 of 6	NP_001350777.1
	TK1	NM_001346663.2		c.316G>A	p.Val106Met	missense	Exon 5 of 7	NP_001333592.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TK1	ENST00000301634.12	TSL:1 MANE Select	c.316G>A	p.Val106Met	missense	Exon 5 of 7	ENSP00000301634.6
	TK1	ENST00000588734.6	TSL:2	c.316G>A	p.Val106Met	missense	Exon 5 of 6	ENSP00000468425.1
	TK1	ENST00000944215.1		c.394G>A	p.Val132Met	missense	Exon 4 of 6	ENSP00000614274.1

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

GnomAD2 exomes AF: 0.00123 AC: 308 AN: 249786 AF XY: 0.00125

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

African (AFR) AF: 0.000807 AC: 27 AN: 33478

American (AMR) AF: 0.00114 AC: 51 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86246

European-Finnish (FIN) AF: 0.0000754 AC: 4 AN: 53064

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00234 AC: 2597 AN: 1111754

Other (OTH) AF: 0.00174 AC: 105 AN: 60354

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

African (AFR) AF: 0.000577 AC: 24 AN: 41582

American (AMR) AF: 0.000523 AC: 8 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68026

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00171 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 v4.9

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
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.045	T
MetaSVM	Uncertain	0.073	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.015	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
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs1132543; hg19: chr17-76171687;