17-7383742-C-T

Variant names:

• chr17-7383742-C-T
• rs1352857517
• NM_003985.6:c.460C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003985.6(TNK1):​c.460C>T​(p.Pro154Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: TNK1 NM_003985.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.874
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1907847).

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.460C>T	p.Pro154Ser	missense	Exon 5 of 13	NP_003976.2	Q13470-2
	TNK1	NM_001251902.3		c.460C>T	p.Pro154Ser	missense	Exon 5 of 13	NP_001238831.1	Q13470-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNK1	ENST00000688331.1	MANE Select	c.460C>T	p.Pro154Ser	missense	Exon 5 of 13	ENSP00000509611.1	Q13470-2
	TNK1	ENST00000576812.5	TSL:1	c.460C>T	p.Pro154Ser	missense	Exon 5 of 13	ENSP00000459799.1	Q13470-1
	TNK1	ENST00000570896.5	TSL:5	c.460C>T	p.Pro154Ser	missense	Exon 6 of 14	ENSP00000458834.1	Q13470-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152276 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000205 AC: 5 AN: 244136 AF XY: 0.0000151

Gnomad AFR exome AF: 0.0000669

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1459888 Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10 AN XY: 726100

African (AFR) AF: 0.0000598 AC: 2 AN: 33440

American (AMR) AF: 0.0000225 AC: 1 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.0000815 AC: 7 AN: 85880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111148

Other (OTH) AF: 0.0000332 AC: 2 AN: 60280

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152276 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74402

African (AFR) AF: 0.00 AC: 0 AN: 41478

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.42	N
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.25	N
PhyloP100		0.87
PrimateAI	Benign	0.35	T
Sift4G	Benign	0.42	T
Polyphen		0.65	P
Vest4		0.32
MutPred		0.33		Gain of phosphorylation at P154 (P = 0.0201)
MVP		0.80
MPC		0.55
ClinPred		0.28	T
GERP RS		0.59
Varity_R		0.11
gMVP		0.32
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1352857517; hg19: chr17-7287061;