rs3761718

chr3-195879148-G-Achr3-195879148-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001382273.1(TNK2):c.915C>T(p.Arg305=) 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:2
• Conservation: PhyloP100: -0.846

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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/exons	MANE	UniProt
TNK2	NM_001382273.1	c.915C>T	p.Arg305=	synonymous_variant	7/16	ENST00000672887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNK2	ENST00000672887.2	c.915C>T	p.Arg305=	synonymous_variant	7/16		NM_001382273.1

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

GnomAD3 exomes AF: 0.0415 AC: 10428 AN: 251052 Hom.: 850 AF XY: 0.0410 AC XY: 5562 AN XY: 135682

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 SAS exome AF: 0.0747

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

Gnomad4 AFR exome AF: 0.00182

Gnomad4 AMR exome AF: 0.0670

Gnomad4 ASJ exome AF: 0.00643

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.0738

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.00151

Gnomad4 OTH exome AF: 0.0240

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

Gnomad4 AFR AF: 0.00351

Gnomad4 AMR AF: 0.0558

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.0796

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.00238

Gnomad4 OTH AF: 0.0176

Alfa AF: 0.00337 Hom.: 7

Bravo AF: 0.0224

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.1
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

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