Variant chr2-171014906-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong

The NM_012290.5(TLK1):c.1279G>A(p.Val427Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00047 in 1,613,980 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00072 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00044 ( 1 hom. )

Consequence

TLK1
NM_012290.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

Variant links:

Genes affected

TLK1 (HGNC:11841): (tousled like kinase 1) The protein encoded by this gene is a serine/threonine kinase that may be involved in the regulation of chromatin assembly. The encoded protein is only active when it is phosphorylated, and this phosphorylation is cell cycle-dependent, with the maximal activity of this protein coming during S phase. The catalytic activity of this protein is diminished by DNA damage and by blockage of DNA replication. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

TLK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, TLK1

BP4

Computational evidence support a benign effect (MetaRNN=0.010010481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLK1	NM_012290.5 linkuse as main transcript	c.1279G>A	p.Val427Ile	missense_variant	13/21	ENST00000431350.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLK1	ENST00000431350.7 linkuse as main transcript	c.1279G>A	p.Val427Ile	missense_variant	13/21	1	NM_012290.5		Q9UKI8-1

Frequencies

GnomAD3 genomes

AF:

0.000729

AC:

111

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000696

AC:

175

AN:

251280

Hom.:

AF XY:

0.000700

AC XY:

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00824

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000396

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000443

AC:

648

AN:

1461682

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

322

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00766

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000288

Gnomad4 OTH exome

AF:

0.000977

GnomAD4 genome

AF:

0.000722

AC:

110

AN:

152298

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000704

Hom.:

Bravo

AF:

0.000892

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000593

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.1279G>A (p.V427I) alteration is located in exon 13 (coding exon 13) of the TLK1 gene. This alteration results from a G to A substitution at nucleotide position 1279, causing the valine (V) at amino acid position 427 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

T;.;.;.

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.010

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.69

N;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.88

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.091

T;T;T;T

Polyphen

0.079

B;B;.;.

Vest4

0.53

MVP

0.52

MPC

1.1

ClinPred

0.018

GERP RS

5.6

Varity_R

0.18

gMVP

0.70

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over