rs1554947

Variant names:

• chr17-7382947-C-T
• rs1554947
• NM_003985.6:c.21C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7382947-C-T
• chr17-7382947-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_003985.6(TNK1):​c.21C>T​(p.Ser7Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,730 control chromosomes in the GnomAD database, including 122,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.32 (9405 hom., cov: 32)
  • Exomes 𝑓: 0.39 (112814 hom.)
• Consequence: TNK1 NM_003985.6 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0930
• Publications: 19 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 17-7382947-C-T is Benign according to our data. Variant chr17-7382947-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060635.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.093 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 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.21C>T	p.Ser7Ser	synonymous	Exon 2 of 13	NP_003976.2	Q13470-2
	TNK1	NM_001251902.3		c.21C>T	p.Ser7Ser	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.21C>T	p.Ser7Ser	synonymous	Exon 2 of 13	ENSP00000509611.1	Q13470-2
	TNK1	ENST00000576812.5	TSL:1	c.21C>T	p.Ser7Ser	synonymous	Exon 2 of 13	ENSP00000459799.1	Q13470-1
	TNK1	ENST00000570896.5	TSL:5	c.21C>T	p.Ser7Ser	synonymous	Exon 3 of 14	ENSP00000458834.1	Q13470-2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48424 AN: 152006 Hom.: 9404 Cov.: 32

Gnomad AFR AF: 0.0895

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.354

GnomAD2 exomes AF: 0.367 AC: 91357 AN: 249148 AF XY: 0.365

Gnomad AFR exome AF: 0.0821

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.453

Gnomad EAS exome AF: 0.469

Gnomad FIN exome AF: 0.439

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.386 AC: 563863 AN: 1461606 Hom.: 112814 Cov.: 52 AF XY: 0.382 AC XY: 277732 AN XY: 727080

African (AFR) AF: 0.0813 AC: 2723 AN: 33480

American (AMR) AF: 0.366 AC: 16357 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 11718 AN: 26130

East Asian (EAS) AF: 0.523 AC: 20772 AN: 39700

South Asian (SAS) AF: 0.225 AC: 19392 AN: 86248

European-Finnish (FIN) AF: 0.440 AC: 23507 AN: 53384

Middle Eastern (MID) AF: 0.406 AC: 2343 AN: 5768

European-Non Finnish (NFE) AF: 0.400 AC: 444762 AN: 1111814

Other (OTH) AF: 0.369 AC: 22289 AN: 60368

GnomAD4 genome AF: 0.318 AC: 48450 AN: 152124 Hom.: 9405 Cov.: 32 AF XY: 0.324 AC XY: 24086 AN XY: 74364

African (AFR) AF: 0.0898 AC: 3730 AN: 41530

American (AMR) AF: 0.400 AC: 6115 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1542 AN: 3472

East Asian (EAS) AF: 0.461 AC: 2380 AN: 5166

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4828

European-Finnish (FIN) AF: 0.457 AC: 4836 AN: 10584

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27540 AN: 67948

Other (OTH) AF: 0.352 AC: 743 AN: 2110

Alfa AF: 0.370 Hom.: 10876

Bravo AF: 0.310

Asia WGS AF: 0.311 AC: 1081 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	-0.44
CADD	Benign	8.3
DANN	Benign	0.67
PhyloP100		-0.093
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: rs1554947; hg19: chr17-7286266; COSMIC: COSV61170778; COSMIC: COSV61170778;