Genetic Variant NM_001382273.1:c.1029C>T (chr3-195878578-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_StrongBP7BS2

The NM_001382273.1(TNK2):c.1029C>T(p.Ile343Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00843 in 1,612,996 control chromosomes in the GnomAD database, including 79 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 63 hom. )

Consequence

TNK2
NM_001382273.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.813

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

infantile-onset mesial temporal lobe epilepsy with severe cognitive regression
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TNK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP6

Variant 3-195878578-G-A is Benign according to our data. Variant chr3-195878578-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.813 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNK2	NM_001382273.1 link	c.1029C>T	p.Ile343Ile	synonymous_variant	Exon 8 of 16	ENST00000672887.2	NP_001369202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNK2	ENST00000672887.2 link	c.1029C>T	p.Ile343Ile	synonymous_variant	Exon 8 of 16		NM_001382273.1	ENSP00000499899.1		A0A5F9ZGX5

Frequencies

GnomAD3 genomes

AF:

0.00873

AC:

1328

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.0791

Gnomad AMR

AF:

0.00845

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0265

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00920

AC:

2269

AN:

246678

AF XY:

0.00927

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00731

Gnomad ASJ exome

AF:

0.00886

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0260

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.0123

GnomAD4 exome

AF:

0.00839

AC:

12263

AN:

1460784

Hom.:

Cov.:

AF XY:

0.00835

AC XY:

6064

AN XY:

726648

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

33470

American (AMR)

AF:

0.00729

AC:

326

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

241

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00164

AC:

141

AN:

86232

European-Finnish (FIN)

AF:

0.0263

AC:

1388

AN:

52792

Middle Eastern (MID)

AF:

0.00634

AC:

AN:

5522

European-Non Finnish (NFE)

AF:

0.00866

AC:

9629

AN:

1111876

Other (OTH)

AF:

0.00754

AC:

455

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

718

1436

2154

2872

3590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

332

664

996

1328

1660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00872

AC:

1328

AN:

152212

Hom.:

Cov.:

AF XY:

0.00953

AC XY:

709

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

41542

American (AMR)

AF:

0.00844

AC:

129

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00145

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0265

AC:

281

AN:

10608

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0104

AC:

710

AN:

68014

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

138

207

276

345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00983

Hom.:

Bravo

AF:

0.00670

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00872

EpiControl

AF:

0.0107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.7

(source)

DANN

Benign

0.88

PhyloP100

-0.81

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over