Variant 11-57301938-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033396.3(TNKS1BP1):c.4840C>T(p.Arg1614Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,514 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TNKS1BP1
NM_033396.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNKS1BP1	NM_033396.3 linkuse as main transcript	c.4840C>T	p.Arg1614Trp	missense_variant	9/12	ENST00000358252.8	NP_203754.2
TNKS1BP1	XM_006718725.4 linkuse as main transcript	c.4840C>T	p.Arg1614Trp	missense_variant	9/12		XP_006718788.1
TNKS1BP1	XM_047427785.1 linkuse as main transcript	c.2812C>T	p.Arg938Trp	missense_variant	5/8		XP_047283741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS1BP1	ENST00000358252.8 linkuse as main transcript	c.4840C>T	p.Arg1614Trp	missense_variant	9/12	1	NM_033396.3	ENSP00000350990	P1	Q9C0C2-1
TNKS1BP1	ENST00000532437.1 linkuse as main transcript	c.4840C>T	p.Arg1614Trp	missense_variant	8/11	1		ENSP00000437271	P1	Q9C0C2-1
TNKS1BP1	ENST00000427750.2 linkuse as main transcript	n.1178C>T		non_coding_transcript_exon_variant	3/6	2
TNKS1BP1	ENST00000528882.5 linkuse as main transcript	c.*3103-1977C>T		intron_variant, NMD_transcript_variant		5		ENSP00000431616

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251190

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461436

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2023

The c.4840C>T (p.R1614W) alteration is located in exon 9 (coding exon 8) of the TNKS1BP1 gene. This alteration results from a C to T substitution at nucleotide position 4840, causing the arginine (R) at amino acid position 1614 to be replaced by a tryptophan (W). 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

0.19

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.089

T;T

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.070

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

1.0

D;D

Vest4

0.54

MVP

0.68

MPC

0.42

ClinPred

1.0

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.65

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over