chr3-195888505-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BA1

The NM_001382273.1(TNK2):c.84T>C(p.Asp28Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,612,956 control chromosomes in the GnomAD database, including 79,118 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12905 hom., cov: 30)

Exomes 𝑓: 0.29 ( 66213 hom. )

Consequence

TNK2
NM_001382273.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.789

Publications

23 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 -17 ACMG points.

BP6

Variant 3-195888505-A-G is Benign according to our data. Variant chr3-195888505-A-G is described in ClinVar as Benign. ClinVar VariationId is 259882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.789 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382273.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNK2	NM_001382273.1	MANE Select	c.84T>C	p.Asp28Asp	synonymous	Exon 2 of 16	NP_001369202.1
TNK2	NM_001387707.1		c.180T>C	p.Asp60Asp	synonymous	Exon 2 of 16	NP_001374636.1
TNK2	NM_001382272.1		c.156T>C	p.Asp52Asp	synonymous	Exon 2 of 16	NP_001369201.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TNK2	ENST00000672887.2	MANE Select	c.84T>C	p.Asp28Asp	synonymous	Exon 2 of 16	ENSP00000499899.1
TNK2	ENST00000428187.7	TSL:1	c.180T>C	p.Asp60Asp	synonymous	Exon 2 of 14	ENSP00000392546.1
TNK2	ENST00000333602.14	TSL:1	c.84T>C	p.Asp28Asp	synonymous	Exon 2 of 15	ENSP00000329425.6

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58818

AN:

151702

Hom.:

12883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.406

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.369

GnomAD2 exomes

AF:

0.337

AC:

84585

AN:

250728

AF XY:

0.329

show subpopulations

Gnomad AFR exome

AF:

0.611

Gnomad AMR exome

AF:

0.387

Gnomad ASJ exome

AF:

0.410

Gnomad EAS exome

AF:

0.441

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.294

AC:

428921

AN:

1461136

Hom.:

66213

Cov.:

AF XY:

0.292

AC XY:

212434

AN XY:

726840

show subpopulations

African (AFR)

AF:

0.608

AC:

20343

AN:

33450

American (AMR)

AF:

0.391

AC:

17456

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

10789

AN:

26112

East Asian (EAS)

AF:

0.428

AC:

16967

AN:

39664

South Asian (SAS)

AF:

0.302

AC:

25992

AN:

86200

European-Finnish (FIN)

AF:

0.293

AC:

15625

AN:

53378

Middle Eastern (MID)

AF:

0.415

AC:

2305

AN:

5558

European-Non Finnish (NFE)

AF:

0.270

AC:

299627

AN:

1111774

Other (OTH)

AF:

0.328

AC:

19817

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

16095

32190

48286

64381

80476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10240

20480

30720

40960

51200

<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:

0.388

AC:

58893

AN:

151820

Hom.:

12905

Cov.:

AF XY:

0.387

AC XY:

28724

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.603

AC:

24971

AN:

41396

American (AMR)

AF:

0.388

AC:

5919

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

1409

AN:

3472

East Asian (EAS)

AF:

0.441

AC:

2278

AN:

5162

South Asian (SAS)

AF:

0.303

AC:

1450

AN:

4780

European-Finnish (FIN)

AF:

0.290

AC:

3047

AN:

10518

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.275

AC:

18698

AN:

67910

Other (OTH)

AF:

0.369

AC:

776

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1717

3434

5151

6868

8585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.316

Hom.:

34098

Bravo

AF:

0.409

Asia WGS

AF:

0.411

AC:

1428

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.297

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.89

(source)

DANN

Benign

0.24

PhyloP100

-0.79

PromoterAI

-0.069

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over