Genetic Variant NM_003985.6:c.*323C>T (chr17-7389407-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003985.6(TNK1):c.*323C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 485,872 control chromosomes in the GnomAD database, including 5,699 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1580 hom., cov: 32)

Exomes 𝑓: 0.14 ( 4119 hom. )

Consequence

TNK1
NM_003985.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.572

Publications

14 publications found

Variant links:

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]

TNK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNK1	NM_003985.6 link	c.*323C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000688331.1	NP_003976.2	Q13470-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNK1	ENST00000688331.1 link	c.*323C>T	3_prime_UTR_variant	Exon 13 of 13		NM_003985.6	ENSP00000509611.1	Q13470-2
TNK1	ENST00000576812.5 link	c.*323C>T	3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000459799.1	Q13470-1
TNK1	ENST00000570896.5 link	c.*323C>T	3_prime_UTR_variant	Exon 14 of 14	5		ENSP00000458834.1	Q13470-2

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19662

AN:

151994

Hom.:

1579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0724

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.274

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.145

AC:

48323

AN:

333760

Hom.:

4119

Cov.:

AF XY:

0.146

AC XY:

24976

AN XY:

171548

show subpopulations

African (AFR)

AF:

0.0764

AC:

777

AN:

10176

American (AMR)

AF:

0.250

AC:

3140

AN:

12554

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

2641

AN:

11246

East Asian (EAS)

AF:

0.202

AC:

5580

AN:

27664

South Asian (SAS)

AF:

0.184

AC:

3095

AN:

16784

European-Finnish (FIN)

AF:

0.137

AC:

3410

AN:

24858

Middle Eastern (MID)

AF:

0.255

AC:

413

AN:

1618

European-Non Finnish (NFE)

AF:

0.125

AC:

26062

AN:

208150

Other (OTH)

AF:

0.155

AC:

3205

AN:

20710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2112

4223

6335

8446

10558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.129

AC:

19671

AN:

152112

Hom.:

1580

Cov.:

AF XY:

0.133

AC XY:

9863

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0724

AC:

3007

AN:

41520

American (AMR)

AF:

0.196

AC:

2983

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

803

AN:

3470

East Asian (EAS)

AF:

0.290

AC:

1495

AN:

5160

South Asian (SAS)

AF:

0.199

AC:

961

AN:

4822

European-Finnish (FIN)

AF:

0.139

AC:

1469

AN:

10588

Middle Eastern (MID)

AF:

0.281

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.122

AC:

8285

AN:

67992

Other (OTH)

AF:

0.170

AC:

357

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

846

1691

2537

3382

4228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.137

Hom.:

2858

Bravo

AF:

0.135

Asia WGS

AF:

0.231

AC:

806

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.9

(source)

DANN

Benign

0.76

PhyloP100

0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over