rs1554948

Variant names:

• chr17-7383007-T-A
• rs1554948
• NM_003985.6:c.81T>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7383007-T-A
• chr17-7383007-T-C
• chr17-7383007-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003985.6(TNK1):​c.81T>A​(p.Leu27Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,613,690 control chromosomes in the GnomAD database, including 171,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (12658 hom., cov: 32)
  • Exomes 𝑓: 0.46 (158692 hom.)
• Consequence: TNK1 NM_003985.6 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.88
• Publications: 33 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-7383007-T-A is Benign according to our data. Variant chr17-7383007-T-A is described in ClinVar as Benign. ClinVar VariationId is 3059508.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

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.81T>A	p.Leu27Leu	synonymous	Exon 2 of 13	NP_003976.2	Q13470-2
	TNK1	NM_001251902.3		c.81T>A	p.Leu27Leu	synonymous	Exon 2 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.81T>A	p.Leu27Leu	synonymous	Exon 2 of 13	ENSP00000509611.1	Q13470-2
	TNK1	ENST00000576812.5	TSL:1	c.81T>A	p.Leu27Leu	synonymous	Exon 2 of 13	ENSP00000459799.1	Q13470-1
	TNK1	ENST00000570896.5	TSL:5	c.81T>A	p.Leu27Leu	synonymous	Exon 3 of 14	ENSP00000458834.1	Q13470-2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60703 AN: 151928 Hom.: 12656 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.379

GnomAD2 exomes AF: 0.417 AC: 104010 AN: 249146 AF XY: 0.432

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.261

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.455

Gnomad OTH exome AF: 0.404

GnomAD4 exome AF: 0.461 AC: 673339 AN: 1461642 Hom.: 158692 Cov.: 65 AF XY: 0.465 AC XY: 338224 AN XY: 727106

African (AFR) AF: 0.313 AC: 10474 AN: 33480

American (AMR) AF: 0.304 AC: 13575 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 9704 AN: 26132

East Asian (EAS) AF: 0.264 AC: 10481 AN: 39700

South Asian (SAS) AF: 0.587 AC: 50669 AN: 86254

European-Finnish (FIN) AF: 0.393 AC: 20999 AN: 53390

Middle Eastern (MID) AF: 0.315 AC: 1818 AN: 5766

European-Non Finnish (NFE) AF: 0.475 AC: 528641 AN: 1111834

Other (OTH) AF: 0.447 AC: 26978 AN: 60370

GnomAD4 genome AF: 0.399 AC: 60728 AN: 152048 Hom.: 12658 Cov.: 32 AF XY: 0.395 AC XY: 29363 AN XY: 74320

African (AFR) AF: 0.322 AC: 13341 AN: 41460

American (AMR) AF: 0.338 AC: 5157 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1308 AN: 3472

East Asian (EAS) AF: 0.274 AC: 1413 AN: 5164

South Asian (SAS) AF: 0.586 AC: 2829 AN: 4826

European-Finnish (FIN) AF: 0.380 AC: 4030 AN: 10592

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31369 AN: 67942

Other (OTH) AF: 0.382 AC: 806 AN: 2108

Alfa AF: 0.399 Hom.: 3760

Bravo AF: 0.382

Asia WGS AF: 0.444 AC: 1546 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs1554948; hg19: chr17-7286326; COSMIC: COSV61170058; COSMIC: COSV61170058;