rs1280356488

Variant names:

• chr17-7383023-A-G
• rs1280356488
• NM_003985.6:c.97A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003985.6(TNK1):​c.97A>G​(p.Thr33Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNK1 NM_003985.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38571537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNK1	NM_003985.6	c.97A>G	p.Thr33Ala	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.97A>G	p.Thr33Ala	missense_variant	Exon 2 of 13		NM_003985.6	ENSP00000509611.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249272 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135238

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.97A>G (p.T33A) alteration is located in exon 2 (coding exon 1) of the TNK1 gene. This alteration results from a A to G substitution at nucleotide position 97, causing the threonine (T) at amino acid position 33 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Uncertain	0.56	T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.90	P;P
Vest4		0.50
MutPred		0.32		Loss of stability (P = 0.1584);Loss of stability (P = 0.1584);
MVP		0.46
MPC		0.24
ClinPred		0.89	D
GERP RS		3.9
Varity_R		0.056
gMVP		0.74

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: rs1280356488; hg19: chr17-7286342;