17-78186962-A-G

Variant names:

• chr17-78186962-A-G
• rs1071664
• NM_003258.5:c.33T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003258.5(TK1):​c.33T>C​(p.Pro11Pro) 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
• Publications: 23 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003258.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TK1	NM_003258.5	MANE Select	c.33T>C	p.Pro11Pro	synonymous	Exon 1 of 7	NP_003249.3
	TK1	NM_001363848.1		c.33T>C	p.Pro11Pro	synonymous	Exon 1 of 6	NP_001350777.1
	TK1	NM_001346663.2		c.33T>C	p.Pro11Pro	synonymous	Exon 1 of 7	NP_001333592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TK1	ENST00000301634.12	TSL:1 MANE Select	c.33T>C	p.Pro11Pro	synonymous	Exon 1 of 7	ENSP00000301634.6
	TK1	ENST00000588734.6	TSL:2	c.33T>C	p.Pro11Pro	synonymous	Exon 1 of 6	ENSP00000468425.1
	TK1	ENST00000586613.1	TSL:3	c.33T>C	p.Pro11Pro	synonymous	Exon 1 of 8	ENSP00000468278.1

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

GnomAD2 exomes AF: 0.464 AC: 88997 AN: 191840 AF XY: 0.449

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 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

African (AFR) AF: 0.708 AC: 22923 AN: 32382

American (AMR) AF: 0.659 AC: 25684 AN: 38970

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 9472 AN: 25538

East Asian (EAS) AF: 0.624 AC: 23144 AN: 37108

South Asian (SAS) AF: 0.417 AC: 33926 AN: 81412

European-Finnish (FIN) AF: 0.413 AC: 20839 AN: 50486

Middle Eastern (MID) AF: 0.375 AC: 2145 AN: 5714

European-Non Finnish (NFE) AF: 0.371 AC: 405478 AN: 1092950

Other (OTH) AF: 0.423 AC: 24935 AN: 58954

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

African (AFR) AF: 0.690 AC: 28594 AN: 41426

American (AMR) AF: 0.573 AC: 8755 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1258 AN: 3466

East Asian (EAS) AF: 0.598 AC: 3020 AN: 5052

South Asian (SAS) AF: 0.423 AC: 2038 AN: 4818

European-Finnish (FIN) AF: 0.410 AC: 4344 AN: 10588

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25457 AN: 67890

Other (OTH) AF: 0.465 AC: 984 AN: 2114

Alfa AF: 0.420 Hom.: 46695

Bravo AF: 0.519

Asia WGS AF: 0.566 AC: 1965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.073
PromoterAI		0.0081	Neutral
Mutation Taster		=99/1	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: rs1071664; hg19: chr17-76183043; COSMIC: COSV107379950; COSMIC: COSV107379950;