chr11-57302518-G-A

Position:

chr11-57302518-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000358252.8(TNKS1BP1):c.4624C>T(p.Arg1542Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,611,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

TNKS1BP1
ENST00000358252.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.512

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:

TNKS1BP1 (HGNC:):

TNKS1BP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07634756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS1BP1	NM_033396.3 linkuse as main transcript	c.4624C>T	p.Arg1542Trp	missense_variant	7/12	ENST00000358252.8	NP_203754.2	Q9C0C2-1A0A024R542
TNKS1BP1	XM_006718725.4 linkuse as main transcript	c.4624C>T	p.Arg1542Trp	missense_variant	7/12		XP_006718788.1	Q9C0C2-1A0A024R542
TNKS1BP1	XM_047427785.1 linkuse as main transcript	c.2596C>T	p.Arg866Trp	missense_variant	3/8		XP_047283741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNKS1BP1	ENST00000358252.8 linkuse as main transcript	c.4624C>T	p.Arg1542Trp	missense_variant	7/12	1	NM_033396.3	ENSP00000350990.3	Q9C0C2-1
TNKS1BP1	ENST00000532437.1 linkuse as main transcript	c.4624C>T	p.Arg1542Trp	missense_variant	6/11	1		ENSP00000437271.1	Q9C0C2-1
TNKS1BP1	ENST00000528882.5 linkuse as main transcript	n.*3103-2557C>T		intron_variant		5		ENSP00000431616.1	E9PKK0
TNKS1BP1	ENST00000427750.2 linkuse as main transcript	n.962C>T		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000686

AC:

AN:

247780

Hom.:

AF XY:

0.0000970

AC XY:

AN XY:

134022

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000874

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000199

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000623

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1459468

Hom.:

Cov.:

AF XY:

0.0000400

AC XY:

AN XY:

725750

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

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

Jul 19, 2022

The c.4624C>T (p.R1542W) alteration is located in exon 7 (coding exon 6) of the TNKS1BP1 gene. This alteration results from a C to T substitution at nucleotide position 4624, causing the arginine (R) at amino acid position 1542 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

0.098

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.65

.;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.038

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.023

D;D

Polyphen

0.049

B;B

Vest4

0.30

MutPred

0.18

Loss of glycosylation at S1541 (P = 0.0264);Loss of glycosylation at S1541 (P = 0.0264);

MVP

0.36

MPC

0.081

ClinPred

0.084

GERP RS

3.5

Varity_R

0.10

gMVP

0.15

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

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