TK1 p.Pro11Pro

Variant names:

• chr17-78186961-C-C
• NM_003258.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr17-78186962--
• chr17-78186962-A-G
• chr17-78186962-A-T
• chr17-78186962-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003258.5(TK1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TK1 NM_003258.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TK1	NM_003258.5	MANE Select	c.		exon_region	Exon 1 of 7	NP_003249.3	A0A384MDV9
	TK1	NM_001363848.1		c.		exon_region	Exon 1 of 6	NP_001350777.1	K7ERV3
	TK1	NM_001346663.2		c.		exon_region	Exon 1 of 7	NP_001333592.1	K7ES52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TK1	ENST00000301634.12	TSL:1 MANE Select	c.		exon_region	Exon 1 of 7	ENSP00000301634.6	P04183
	TK1	ENST00000588734.6	TSL:2	c.		exon_region	Exon 1 of 6	ENSP00000468425.1	K7ERV3
	TK1	ENST00000944215.1		c.		exon_region	Exon 1 of 6	ENSP00000614274.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.073

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-76183042;