17-7383694-TC-T

Variant names:

• chr17-7383694-TC-T
• rs567484359
• NM_003985.6:c.427-9delC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_003985.6(TNK1):​c.427-9delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,610,118 control chromosomes in the GnomAD database, including 28 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0033 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (27 hom.)
• Consequence: TNK1 NM_003985.6 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.105
• Publications: 0 publications found

Genes affected

TNK1 (HGNC:11940): (tyrosine kinase non receptor 1) The protein encoded by this gene belongs to the tyrosine protein kinase family. Tyrosine protein kinases are important regulators of intracellular signal transduction pathways, mediating cellular proliferation, survival, and development. This gene is highly expressed in fetal tissues and at lower levels in few adult tissues, thus may function in signaling pathways utilized broadly during fetal development, and more selectively in adult tissues. It plays a negative regulatory role in the Ras-Raf1-MAPK pathway, and knockout mice have been shown to develop spontaneous tumors, suggesting a role as a tumor suppressor gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 17-7383694-TC-T is Benign according to our data. Variant chr17-7383694-TC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3053179.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003985.6. 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
	TNK1	NM_003985.6	MANE Select	c.427-9delC		intron	N/A	NP_003976.2	Q13470-2
	TNK1	NM_001251902.3		c.427-9delC		intron	N/A	NP_001238831.1	Q13470-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNK1	ENST00000688331.1	MANE Select	c.427-9delC		intron	N/A	ENSP00000509611.1	Q13470-2
	TNK1	ENST00000576812.5	TSL:1	c.427-9delC		intron	N/A	ENSP00000459799.1	Q13470-1
	TNK1	ENST00000570896.5	TSL:5	c.427-9delC		intron	N/A	ENSP00000458834.1	Q13470-2

Frequencies

GnomAD3 genomes AF: 0.00326 AC: 496 AN: 152100 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00600

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00252 AC: 609 AN: 241212 AF XY: 0.00236

Gnomad AFR exome AF: 0.000406

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00154

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00119

Gnomad NFE exome AF: 0.00457

Gnomad OTH exome AF: 0.00238

GnomAD4 exome AF: 0.00452 AC: 6583 AN: 1457898 Hom.: 27 Cov.: 34 AF XY: 0.00436 AC XY: 3158 AN XY: 724940

African (AFR) AF: 0.000599 AC: 20 AN: 33386

American (AMR) AF: 0.00152 AC: 67 AN: 44186

Ashkenazi Jewish (ASJ) AF: 0.00185 AC: 48 AN: 25964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.00 AC: 0 AN: 85616

European-Finnish (FIN) AF: 0.00167 AC: 89 AN: 53202

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.00549 AC: 6090 AN: 1110012

Other (OTH) AF: 0.00444 AC: 267 AN: 60192

GnomAD4 genome AF: 0.00326 AC: 496 AN: 152220 Hom.: 1 Cov.: 33 AF XY: 0.00293 AC XY: 218 AN XY: 74412

African (AFR) AF: 0.000530 AC: 22 AN: 41534

American (AMR) AF: 0.00288 AC: 44 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00600 AC: 408 AN: 67998

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00498 Hom.: 0

Bravo AF: 0.00319

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TNK1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs567484359; hg19: chr17-7287013;