Variant 17-7383007-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_003985.6(TNK1):c.81T>A(p.Leu27Leu) 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 (no stars).

Frequency

Genomes: 𝑓 0.40 ( 12658 hom., cov: 32)

Exomes 𝑓: 0.46 ( 158692 hom. )

Consequence

TNK1
NM_003985.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.88

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 -14 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
TNK1	NM_003985.6 link	c.81T>A	p.Leu27Leu	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.81T>A	p.Leu27Leu	synonymous_variant	Exon 2 of 13		NM_003985.6	ENSP00000509611.1		Q13470-2

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60703

AN:

151928

Hom.:

12656

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.465

AC XY:

338224

AN XY:

727106

show subpopulations

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.:

AF XY:

0.395

AC XY:

29363

AN XY:

74320

show subpopulations

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: no assertion criteria provided

LINK: link

Submissions by phenotype

TNK1-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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