rs4668368

Positions:

• chr2-171069652-T-A
• chr2-171069652-T-G

Variant summary

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

The NM_012290.5(TLK1):​c.331-8496A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,010 control chromosomes in the GnomAD database, including 26,935 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 0.57 (26935 hom., cov: 31)
• Consequence: TLK1 NM_012290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLK1	NM_012290.5	c.331-8496A>T		intron_variant		ENST00000431350.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLK1	ENST00000431350.7	c.331-8496A>T		intron_variant		1	NM_012290.5

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87192 AN: 151892 Hom.: 26919 Cov.: 31

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.574 AC: 87238 AN: 152010 Hom.: 26935 Cov.: 31 AF XY: 0.585 AC XY: 43503 AN XY: 74304

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.588

Alfa AF: 0.595 Hom.: 3482

Bravo AF: 0.558

Asia WGS AF: 0.843 AC: 2932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.69

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: rs4668368; hg19: chr2-171926162;