Variant chr3-195868534-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001382273.1(TNK2):c.1764C>T(p.Phe588=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 1,564,262 control chromosomes in the GnomAD database, including 3,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 332 hom., cov: 33)

Exomes 𝑓: 0.061 ( 2874 hom. )

Consequence

TNK2
NM_001382273.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.821

Variant links:

Genes affected

TNK2 (HGNC:19297): (tyrosine kinase non receptor 2) This gene encodes a tyrosine kinase that binds Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]

TNK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-195868534-G-A is Benign according to our data. Variant chr3-195868534-G-A is described in ClinVar as [Benign]. Clinvar id is 259872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.821 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNK2	NM_001382273.1 linkuse as main transcript	c.1764C>T	p.Phe588=	synonymous_variant	13/16	ENST00000672887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNK2	ENST00000672887.2 linkuse as main transcript	c.1764C>T	p.Phe588=	synonymous_variant	13/16		NM_001382273.1

Frequencies

GnomAD3 genomes

AF:

0.0607

AC:

9231

AN:

152090

Hom.:

332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0847

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0322

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.0804

Gnomad SAS

AF:

0.0614

Gnomad FIN

AF:

0.0357

Gnomad MID

AF:

0.0321

Gnomad NFE

AF:

0.0571

Gnomad OTH

AF:

0.0468

GnomAD3 exomes

AF:

0.0544

AC:

9235

AN:

169668

Hom.:

290

AF XY:

0.0553

AC XY:

5273

AN XY:

95316

show subpopulations

Gnomad AFR exome

AF:

0.0894

Gnomad AMR exome

AF:

0.0175

Gnomad ASJ exome

AF:

0.0260

Gnomad EAS exome

AF:

0.0831

Gnomad SAS exome

AF:

0.0672

Gnomad FIN exome

AF:

0.0351

Gnomad NFE exome

AF:

0.0594

Gnomad OTH exome

AF:

0.0498

GnomAD4 exome

AF:

0.0610

AC:

86078

AN:

1412054

Hom.:

2874

Cov.:

AF XY:

0.0609

AC XY:

42674

AN XY:

701090

show subpopulations

Gnomad4 AFR exome

AF:

0.0899

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.0257

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.0691

Gnomad4 FIN exome

AF:

0.0380

Gnomad4 NFE exome

AF:

0.0609

Gnomad4 OTH exome

AF:

0.0583

GnomAD4 genome

AF:

0.0607

AC:

9242

AN:

152208

Hom.:

332

Cov.:

AF XY:

0.0602

AC XY:

4479

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0848

Gnomad4 AMR

AF:

0.0321

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.0802

Gnomad4 SAS

AF:

0.0612

Gnomad4 FIN

AF:

0.0357

Gnomad4 NFE

AF:

0.0571

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0542

Hom.:

Bravo

AF:

0.0632

Asia WGS

AF:

0.0710

AC:

247

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.15

DANN

Benign

0.68

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