rs1065769

Positions:

• chr17-78174654-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
TK1	NM_003258.5	c.*105G>A		3_prime_UTR_variant	7/7	ENST00000301634.12	NP_003249.3
TK1	NM_001363848.1	c.*105G>A		3_prime_UTR_variant	6/6		NP_001350777.1
TK1	NM_001346663.2	c.*105G>A		3_prime_UTR_variant	7/7		NP_001333592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TK1	ENST00000301634	c.*105G>A		3_prime_UTR_variant	7/7	1	NM_003258.5	ENSP00000301634.6
TK1	ENST00000588734	c.*105G>A		3_prime_UTR_variant	6/6	2		ENSP00000468425.1
TK1	ENST00000590862.5	c.*105G>A		downstream_gene_variant		3		ENSP00000468556.1

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

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.309

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

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.302

Alfa AF: 0.320 Hom.: 9293

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1065769; hg19: chr17-76170735;