rs754747109
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003258.5(TK1):c.499G>T(p.Gly167Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
TK1
NM_003258.5 missense
NM_003258.5 missense
Scores
7
8
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.76
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.821
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TK1 | NM_003258.5 | c.499G>T | p.Gly167Cys | missense_variant | Exon 6 of 7 | ENST00000301634.12 | NP_003249.3 | |
| TK1 | NM_001363848.1 | c.499G>T | p.Gly167Cys | missense_variant | Exon 6 of 6 | NP_001350777.1 | ||
| TK1 | NM_001346663.2 | c.499G>T | p.Gly167Cys | missense_variant | Exon 6 of 7 | NP_001333592.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152024Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome 0.00000658 AC: 1AN: 152024Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74248
GnomAD4 genome
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74248
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.;.
REVEL
Uncertain
Sift
Benign
D;.;.;.
Sift4G
Benign
T;D;D;.
Polyphen
P;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.0126);Loss of disorder (P = 0.0126);Loss of disorder (P = 0.0126);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at