NM_001382273.1:c.1029C>T

Variant names:

• chr3-195878578-G-A
• rs55842111
• NM_001382273.1:c.1029C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.813
• Publications: 3 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
• genetic generalized epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNK2	NM_001382273.1	MANE Select	c.1029C>T	p.Ile343Ile	synonymous	Exon 8 of 16	NP_001369202.1	A0A5F9ZGX5
	TNK2	NM_001387707.1		c.1125C>T	p.Ile375Ile	synonymous	Exon 8 of 16	NP_001374636.1
	TNK2	NM_001382272.1		c.1101C>T	p.Ile367Ile	synonymous	Exon 8 of 16	NP_001369201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNK2	ENST00000672887.2	MANE Select	c.1029C>T	p.Ile343Ile	synonymous	Exon 8 of 16	ENSP00000499899.1	A0A5F9ZGX5
	TNK2	ENST00000428187.7	TSL:1	c.1125C>T	p.Ile375Ile	synonymous	Exon 8 of 14	ENSP00000392546.1	C9J1X3
	TNK2	ENST00000333602.14	TSL:1	c.1029C>T	p.Ile343Ile	synonymous	Exon 8 of 15	ENSP00000329425.6	Q07912-1

Frequencies

GnomAD3 genomes AF: 0.00873 AC: 1328 AN: 152094 Hom.: 16 Cov.: 32

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

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.: 63 Cov.: 32 AF XY: 0.00835 AC XY: 6064 AN XY: 726648

African (AFR) AF: 0.00143 AC: 48 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: 0 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: 35 AN: 5522

European-Non Finnish (NFE) AF: 0.00866 AC: 9629 AN: 1111876

Other (OTH) AF: 0.00754 AC: 455 AN: 60342

GnomAD4 genome AF: 0.00872 AC: 1328 AN: 152212 Hom.: 16 Cov.: 32 AF XY: 0.00953 AC XY: 709 AN XY: 74426

African (AFR) AF: 0.00185 AC: 77 AN: 41542

American (AMR) AF: 0.00844 AC: 129 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.0265 AC: 281 AN: 10608

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0104 AC: 710 AN: 68014

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00983 Hom.: 6

Bravo AF: 0.00670

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00872

EpiControl AF: 0.0107

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.7
DANN	Benign	0.88
PhyloP100		-0.81
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs55842111; hg19: chr3-195605449; COSMIC: COSV100361846; COSMIC: COSV100361846;