17-78186962-A-G

Position:

• chr17-78186962-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003258.5(TK1):​c.33T>C​(p.Pro11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,575,348 control chromosomes in the GnomAD database, including 138,400 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 0.49 (19837 hom., cov: 30)
  • Exomes 𝑓: 0.40 (118563 hom.)
• Consequence: TK1 NM_003258.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.073 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TK1	NM_003258.5	c.33T>C	p.Pro11=	synonymous_variant	1/7	ENST00000301634.12
TK1	NM_001363848.1	c.33T>C	p.Pro11=	synonymous_variant	1/6
TK1	NM_001346663.2	c.33T>C	p.Pro11=	synonymous_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TK1	ENST00000301634.12	c.33T>C	p.Pro11=	synonymous_variant	1/7	1	NM_003258.5	P1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74704 AN: 151716 Hom.: 19777 Cov.: 30

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.463

GnomAD3 exomes AF: 0.464 AC: 88997 AN: 191840 Hom.: 22212 AF XY: 0.449 AC XY: 46394 AN XY: 103298

Gnomad AFR exome AF: 0.700

Gnomad AMR exome AF: 0.674

Gnomad ASJ exome AF: 0.373

Gnomad EAS exome AF: 0.607

Gnomad SAS exome AF: 0.417

Gnomad FIN exome AF: 0.418

Gnomad NFE exome AF: 0.371

Gnomad OTH exome AF: 0.430

GnomAD4 exome AF: 0.399 AC: 568546 AN: 1423514 Hom.: 118563 Cov.: 54 AF XY: 0.398 AC XY: 280595 AN XY: 704852

Gnomad4 AFR exome AF: 0.708

Gnomad4 AMR exome AF: 0.659

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.493 AC: 74828 AN: 151834 Hom.: 19837 Cov.: 30 AF XY: 0.495 AC XY: 36708 AN XY: 74194

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.465

Alfa AF: 0.403 Hom.: 20967

Bravo AF: 0.519

Asia WGS AF: 0.566 AC: 1965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.75

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: rs1071664; hg19: chr17-76183043;