Genetic Variant TNKS1BP1:p.Leu1497Leu (chr11-57302651-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_033396.3(TNKS1BP1):c.4491G>A(p.Leu1497Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,610,430 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 25 hom. )

Consequence

TNKS1BP1
NM_033396.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.356

Publications

1 publications found

Variant links:

Genes affected

TNKS1BP1 (HGNC:19081): (tankyrase 1 binding protein 1) Enables ankyrin repeat binding activity and enzyme binding activity. Involved in cellular response to ionizing radiation; double-strand break repair; and positive regulation of protein phosphorylation. Located in several cellular components, including actin cytoskeleton; adherens junction; and heterochromatin. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

TNKS1BP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 11-57302651-C-T is Benign according to our data. Variant chr11-57302651-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2641791.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.356 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033396.3. 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
	TNKS1BP1	NM_033396.3	MANE Select	c.4491G>A	p.Leu1497Leu	synonymous	Exon 7 of 12	NP_203754.2	Q9C0C2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNKS1BP1	ENST00000358252.8	TSL:1 MANE Select	c.4491G>A	p.Leu1497Leu	synonymous	Exon 7 of 12	ENSP00000350990.3	Q9C0C2-1
TNKS1BP1	ENST00000532437.1	TSL:1	c.4491G>A	p.Leu1497Leu	synonymous	Exon 6 of 11	ENSP00000437271.1	Q9C0C2-1
TNKS1BP1	ENST00000528882.5	TSL:5	n.*3103-2690G>A		intron	N/A	ENSP00000431616.1	E9PKK0

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

273

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00239

AC:

586

AN:

245312

AF XY:

0.00219

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.00300

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000512

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.00142

AC:

2065

AN:

1458178

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1041

AN XY:

725324

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

33450

American (AMR)

AF:

0.00291

AC:

130

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.0303

AC:

789

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.000303

AC:

AN:

85846

European-Finnish (FIN)

AF:

0.0000972

AC:

AN:

51416

Middle Eastern (MID)

AF:

0.00993

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.000689

AC:

766

AN:

1111226

Other (OTH)

AF:

0.00383

AC:

231

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

126

252

379

505

631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00179

AC:

273

AN:

152252

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

41538

American (AMR)

AF:

0.00183

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0352

AC:

122

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000956

AC:

AN:

68008

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00379

Hom.:

Bravo

AF:

0.00216

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00208

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.96

(source)

DANN

Benign

0.52

PhyloP100

-0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over