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GeneBe

17-78174870-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003258.5(TK1):c.594C>T(p.Ala198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,613,828 control chromosomes in the GnomAD database, including 283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 156 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 127 hom. )

Consequence

TK1
NM_003258.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.61
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-78174870-G-A is Benign according to our data. Variant chr17-78174870-G-A is described in ClinVar as [Benign]. Clinvar id is 785585.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.61 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TK1NM_003258.5 linkuse as main transcriptc.594C>T p.Ala198= synonymous_variant 7/7 ENST00000301634.12
TK1NM_001363848.1 linkuse as main transcriptc.693C>T p.Ala231= synonymous_variant 6/6
TK1NM_001346663.2 linkuse as main transcriptc.514-82C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TK1ENST00000301634.12 linkuse as main transcriptc.594C>T p.Ala198= synonymous_variant 7/71 NM_003258.5 P1
TK1ENST00000588734.5 linkuse as main transcriptc.693C>T p.Ala231= synonymous_variant 6/62
TK1ENST00000590430.5 linkuse as main transcriptc.*335C>T 3_prime_UTR_variant 5/53
TK1ENST00000590862.5 linkuse as main transcriptc.514-82C>T intron_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0227
AC:
3453
AN:
152216
Hom.:
156
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0795
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00707
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.0148
GnomAD3 exomes
AF:
0.00588
AC:
1457
AN:
247636
Hom.:
67
AF XY:
0.00410
AC XY:
551
AN XY:
134262
show subpopulations
Gnomad AFR exome
AF:
0.0823
Gnomad AMR exome
AF:
0.00284
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000543
Gnomad OTH exome
AF:
0.00246
GnomAD4 exome
AF:
0.00229
AC:
3344
AN:
1461494
Hom.:
127
Cov.:
33
AF XY:
0.00194
AC XY:
1407
AN XY:
727010
show subpopulations
Gnomad4 AFR exome
AF:
0.0842
Gnomad4 AMR exome
AF:
0.00331
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000432
Gnomad4 OTH exome
AF:
0.00480
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0227
AC:
3458
AN:
152334
Hom.:
156
Cov.:
32
AF XY:
0.0222
AC XY:
1656
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0793
Gnomad4 AMR
AF:
0.00706
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.0147
Alfa
AF:
0.00849
Hom.:
22
Bravo
AF:
0.0256
Asia WGS
AF:
0.00491
AC:
18
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
Cadd
Benign
1.3
Dann
Benign
0.87
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1065767; hg19: chr17-76170951; API