rs1065769

Variant names:

• chr17-78174654-C-T
• rs1065769
• NM_003258.5:c.*105G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003258.5(TK1):​c.*105G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,329,312 control chromosomes in the GnomAD database, including 67,808 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 0.33 (8345 hom., cov: 33)
  • Exomes 𝑓: 0.31 (59463 hom.)
• Consequence: TK1 NM_003258.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 20 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TK1	NM_003258.5	c.*105G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000301634.12	NP_003249.3
TK1	NM_001363848.1	c.*105G>A		3_prime_UTR_variant	Exon 6 of 6		NP_001350777.1
TK1	NM_001346663.2	c.*105G>A		3_prime_UTR_variant	Exon 7 of 7		NP_001333592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TK1	ENST00000301634.12	c.*105G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_003258.5	ENSP00000301634.6
TK1	ENST00000588734.6	c.*105G>A		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000468425.1
TK1	ENST00000590862.5	c.*105G>A		downstream_gene_variant		3		ENSP00000468556.1
TK1	ENST00000590430.5	c.*551G>A		downstream_gene_variant		3		ENSP00000467121.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49749 AN: 151998 Hom.: 8336 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.315 AC: 370603 AN: 1177196 Hom.: 59463 Cov.: 17 AF XY: 0.313 AC XY: 180513 AN XY: 577136

African (AFR) AF: 0.379 AC: 9790 AN: 25844

American (AMR) AF: 0.248 AC: 5425 AN: 21840

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 5123 AN: 18448

East Asian (EAS) AF: 0.174 AC: 5954 AN: 34260

South Asian (SAS) AF: 0.265 AC: 16343 AN: 61646

European-Finnish (FIN) AF: 0.362 AC: 13169 AN: 36408

Middle Eastern (MID) AF: 0.251 AC: 889 AN: 3538

European-Non Finnish (NFE) AF: 0.323 AC: 298533 AN: 925374

Other (OTH) AF: 0.309 AC: 15377 AN: 49838

GnomAD4 genome AF: 0.327 AC: 49797 AN: 152116 Hom.: 8345 Cov.: 33 AF XY: 0.325 AC XY: 24159 AN XY: 74352

African (AFR) AF: 0.380 AC: 15745 AN: 41478

American (AMR) AF: 0.281 AC: 4303 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3466

East Asian (EAS) AF: 0.174 AC: 902 AN: 5170

South Asian (SAS) AF: 0.263 AC: 1271 AN: 4832

European-Finnish (FIN) AF: 0.353 AC: 3738 AN: 10588

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21974 AN: 67974

Other (OTH) AF: 0.302 AC: 638 AN: 2112

Alfa AF: 0.320 Hom.: 12005

Bravo AF: 0.322

Asia WGS AF: 0.226 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.57
PhyloP100		0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1065769; hg19: chr17-76170735;