rs1056726

chr3-195868534-G-A

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.821

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=-0.82).
• 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	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	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.: 33

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

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.: 45 AF XY: 0.0609 AC XY: 42674 AN XY: 701090

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.: 33 AF XY: 0.0602 AC XY: 4479 AN XY: 74408

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.: 65

Bravo AF: 0.0632

Asia WGS AF: 0.0710 AC: 247 AN: 3476

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

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

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

Other links and lift over

dbSNP: rs1056726; hg19: chr3-195595405; COSMIC: COSV57368889; COSMIC: COSV57368889;