rs1554948

chr17-7383007-T-Achr17-7383007-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003985.6(TNK1):c.81T>A(p.Leu27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,613,690 control chromosomes in the GnomAD database, including 171,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12658 hom., cov: 32)
  • Exomes 𝑓: 0.46 (158692 hom.)
• Consequence: TNK1 NM_003985.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.88

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-7383007-T-A is Benign according to our data. Variant chr17-7383007-T-A is described in ClinVar as [Benign]. Clinvar id is 3059508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNK1	NM_003985.6	c.81T>A	p.Leu27=	synonymous_variant	2/13	ENST00000688331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNK1	ENST00000688331.1	c.81T>A	p.Leu27=	synonymous_variant	2/13		NM_003985.6	P3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60703 AN: 151928 Hom.: 12656 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.417 AC: 104010 AN: 249146 Hom.: 22868 AF XY: 0.432 AC XY: 58411 AN XY: 135172

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.261

Gnomad SAS exome AF: 0.591

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.455

Gnomad OTH exome AF: 0.404

GnomAD4 exome AF: 0.461 AC: 673339 AN: 1461642 Hom.: 158692 Cov.: 65 AF XY: 0.465 AC XY: 338224 AN XY: 727106

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.264

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.399 AC: 60728 AN: 152048 Hom.: 12658 Cov.: 32 AF XY: 0.395 AC XY: 29363 AN XY: 74320

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.382

Alfa AF: 0.399 Hom.: 3760

Bravo AF: 0.382

Asia WGS AF: 0.444 AC: 1546 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TNK1-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	1.9
Dann	Benign	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

Other links and lift over

dbSNP: rs1554948; hg19: chr17-7286326; COSMIC: COSV61170058; COSMIC: COSV61170058;