rs10183486

Variant names:

• chr2-171134461-C-T
• rs10183486
• NM_012290.5:c.140-16604G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012290.5(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 NM_012290.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 31 publications found

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]

LOC124906092 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TLK1	NM_012290.5	c.140-16604G>A		intron_variant	Intron 1 of 20	ENST00000431350.7	NP_036422.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLK1	ENST00000431350.7	c.140-16604G>A		intron_variant	Intron 1 of 20	1	NM_012290.5	ENSP00000411099.2

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

African (AFR) AF: 0.587 AC: 24324 AN: 41458

American (AMR) AF: 0.329 AC: 5021 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1133 AN: 3472

East Asian (EAS) AF: 0.0513 AC: 266 AN: 5182

South Asian (SAS) AF: 0.164 AC: 791 AN: 4828

European-Finnish (FIN) AF: 0.293 AC: 3094 AN: 10542

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.366 AC: 24859 AN: 67954

Other (OTH) AF: 0.401 AC: 847 AN: 2112

Alfa AF: 0.367 Hom.: 17074

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10183486; hg19: chr2-171990971;