chr2-171134461-C-T

Position:

• chr2-171134461-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000431350.7(TLK1):​c.140-16604G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,008 control chromosomes in the GnomAD database, including 13,739 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 0.40 (13739 hom., cov: 32)
• Consequence: TLK1 ENST00000431350.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

Genes affected

LOC124906092 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124906092	XM_047446755.1	c.-10489G>A		5_prime_UTR_variant	1/1		XP_047302711.1
TLK1	NM_012290.5	c.140-16604G>A		intron_variant		ENST00000431350.7	NP_036422.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLK1	ENST00000431350.7	c.140-16604G>A		intron_variant		1	NM_012290.5	ENSP00000411099

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60975 AN: 151890 Hom.: 13704 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0512

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.405

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61053 AN: 152008 Hom.: 13739 Cov.: 32 AF XY: 0.391 AC XY: 29024 AN XY: 74286

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.0513

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.401

Alfa AF: 0.373 Hom.: 1952

Bravo AF: 0.418

Asia WGS AF: 0.156 AC: 543 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.39

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

Other links and lift over

dbSNP: rs10183486; hg19: chr2-171990971;