Variant 17-7382947-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_003985.6(TNK1):c.21C>T(p.Ser7Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,730 control chromosomes in the GnomAD database, including 122,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.32 ( 9405 hom., cov: 32)

Exomes 𝑓: 0.39 ( 112814 hom. )

Consequence

TNK1
NM_003985.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0930

Variant links:

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]

TNK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 17-7382947-C-T is Benign according to our data. Variant chr17-7382947-C-T is described in ClinVar as [Benign]. Clinvar id is 3060635.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.093 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNK1	NM_003985.6 link	c.21C>T	p.Ser7Ser	synonymous_variant	Exon 2 of 13	ENST00000688331.1	NP_003976.2	Q13470-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNK1	ENST00000688331.1 link	c.21C>T	p.Ser7Ser	synonymous_variant	Exon 2 of 13		NM_003985.6	ENSP00000509611.1		Q13470-2

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48424

AN:

152006

Hom.:

9404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0895

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.461

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.354

GnomAD3 exomes

AF:

0.367

AC:

91357

AN:

249148

Hom.:

18118

AF XY:

0.365

AC XY:

49360

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.0821

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.453

Gnomad EAS exome

AF:

0.469

Gnomad SAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.386

AC:

563863

AN:

1461606

Hom.:

112814

Cov.:

AF XY:

0.382

AC XY:

277732

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.0813

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.448

Gnomad4 EAS exome

AF:

0.523

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.400

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.318

AC:

48450

AN:

152124

Hom.:

9405

Cov.:

AF XY:

0.324

AC XY:

24086

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0898

Gnomad4 AMR

AF:

0.400

Gnomad4 ASJ

AF:

0.444

Gnomad4 EAS

AF:

0.461

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.405

Gnomad4 OTH

AF:

0.352

Alfa

AF:

0.372

Hom.:

8292

Bravo

AF:

0.310

Asia WGS

AF:

0.311

AC:

1081

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TNK1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

-0.44

CADD

Benign

8.3

DANN

Benign

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over