rs3761718

Variant names:

• chr3-195879148-G-A
• rs3761718
• NM_001382273.1:c.915C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-195879148-G-A
• chr3-195879148-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001382273.1(TNK2):​c.915C>T​(p.Arg305Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,613,780 control chromosomes in the GnomAD database, including 2,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (235 hom., cov: 32)
  • Exomes 𝑓: 0.017 (2005 hom.)
• Consequence: TNK2 NM_001382273.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.846
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.023).
• BP6: Variant 3-195879148-G-A is Benign according to our data. Variant chr3-195879148-G-A is described in ClinVar as [Benign]. Clinvar id is 259883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.846 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNK2	NM_001382273.1	c.915C>T	p.Arg305Arg	synonymous_variant	Exon 7 of 16	ENST00000672887.2	NP_001369202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNK2	ENST00000672887.2	c.915C>T	p.Arg305Arg	synonymous_variant	Exon 7 of 16		NM_001382273.1	ENSP00000499899.1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3070 AN: 152146 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00238

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0415 AC: 10428 AN: 251052 AF XY: 0.0410

Gnomad AFR exome AF: 0.00277

Gnomad AMR exome AF: 0.0706

Gnomad ASJ exome AF: 0.00665

Gnomad EAS exome AF: 0.259

Gnomad FIN exome AF: 0.0149

Gnomad NFE exome AF: 0.00287

Gnomad OTH exome AF: 0.0282

GnomAD4 exome AF: 0.0166 AC: 24315 AN: 1461514 Hom.: 2005 Cov.: 31 AF XY: 0.0180 AC XY: 13108 AN XY: 727048

African (AFR) AF: 0.00182 AC: 61 AN: 33480

American (AMR) AF: 0.0670 AC: 2995 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00643 AC: 168 AN: 26134

East Asian (EAS) AF: 0.271 AC: 10768 AN: 39698

South Asian (SAS) AF: 0.0738 AC: 6366 AN: 86256

European-Finnish (FIN) AF: 0.0150 AC: 797 AN: 53114

Middle Eastern (MID) AF: 0.00486 AC: 28 AN: 5766

European-Non Finnish (NFE) AF: 0.00151 AC: 1682 AN: 1111964

Other (OTH) AF: 0.0240 AC: 1450 AN: 60388

GnomAD4 genome AF: 0.0202 AC: 3069 AN: 152266 Hom.: 235 Cov.: 32 AF XY: 0.0239 AC XY: 1780 AN XY: 74454

African (AFR) AF: 0.00351 AC: 146 AN: 41546

American (AMR) AF: 0.0558 AC: 853 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3466

East Asian (EAS) AF: 0.258 AC: 1333 AN: 5176

South Asian (SAS) AF: 0.0796 AC: 384 AN: 4822

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00238 AC: 162 AN: 68022

Other (OTH) AF: 0.0176 AC: 37 AN: 2108

Alfa AF: 0.0102 Hom.: 92

Bravo AF: 0.0224

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.1
DANN	Benign	0.77
PhyloP100		-0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3761718; hg19: chr3-195606019; COSMIC: COSV57368208; COSMIC: COSV57368208;