NM_003985.6:c.115G>C

Variant names:

• chr17-7383041-G-C
• rs200735706
• NM_003985.6:c.115G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003985.6(TNK1):​c.115G>C​(p.Asp39His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNK1 NM_003985.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24170414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNK1	NM_003985.6	c.115G>C	p.Asp39His	missense_variant	Exon 2 of 13	ENST00000688331.1	NP_003976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNK1	ENST00000688331.1	c.115G>C	p.Asp39His	missense_variant	Exon 2 of 13		NM_003985.6	ENSP00000509611.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	.;D
Eigen	Benign	0.18
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Benign	0.40	T
Sift4G	Uncertain	0.013	D;D
Polyphen		0.90	P;P
Vest4		0.21
MutPred		0.33		Loss of ubiquitination at K42 (P = 0.063);Loss of ubiquitination at K42 (P = 0.063);
MVP		0.57
MPC		0.23
ClinPred		0.91	D
GERP RS		2.0
Varity_R		0.064
gMVP		0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs200735706; hg19: chr17-7286360;