rs2075760

Positions:

• chr17-7389407-C-T

Variant summary

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

The NM_003985.6(TNK1):​c.*323C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 485,872 control chromosomes in the GnomAD database, including 5,699 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 0.13 (1580 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4119 hom.)
• Consequence: TNK1 NM_003985.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572

Genes affected

TNK1 (HGNC:11940): (tyrosine kinase non receptor 1) The protein encoded by this gene belongs to the tyrosine protein kinase family. Tyrosine protein kinases are important regulators of intracellular signal transduction pathways, mediating cellular proliferation, survival, and development. This gene is highly expressed in fetal tissues and at lower levels in few adult tissues, thus may function in signaling pathways utilized broadly during fetal development, and more selectively in adult tissues. It plays a negative regulatory role in the Ras-Raf1-MAPK pathway, and knockout mice have been shown to develop spontaneous tumors, suggesting a role as a tumor suppressor gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNK1	NM_003985.6	c.*323C>T		3_prime_UTR_variant	13/13	ENST00000688331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNK1	ENST00000688331.1	c.*323C>T		3_prime_UTR_variant	13/13		NM_003985.6	P3
TNK1	ENST00000576812.5	c.*323C>T		3_prime_UTR_variant	13/13	1		A1
TNK1	ENST00000570896.5	c.*323C>T		3_prime_UTR_variant	14/14	5		P3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19662 AN: 151994 Hom.: 1579 Cov.: 32

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.145 AC: 48323 AN: 333760 Hom.: 4119 Cov.: 0 AF XY: 0.146 AC XY: 24976 AN XY: 171548

Gnomad4 AFR exome AF: 0.0764

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.202

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.129 AC: 19671 AN: 152112 Hom.: 1580 Cov.: 32 AF XY: 0.133 AC XY: 9863 AN XY: 74334

Gnomad4 AFR AF: 0.0724

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.170

Alfa AF: 0.139 Hom.: 2294

Bravo AF: 0.135

Asia WGS AF: 0.231 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.9
DANN	Benign	0.76

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: rs2075760; hg19: chr17-7292726;