Variant 11-57302715-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000358252.8(TNKS1BP1):c.4427C>T(p.Ser1476Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000076 in 1,447,268 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

TNKS1BP1
ENST00000358252.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.211

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062004596).

BP6

Variant 11-57302715-G-A is Benign according to our data. Variant chr11-57302715-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2533686.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS1BP1	NM_033396.3 linkuse as main transcript	c.4427C>T	p.Ser1476Leu	missense_variant	7/12	ENST00000358252.8	NP_203754.2	Q9C0C2-1A0A024R542
TNKS1BP1	XM_006718725.4 linkuse as main transcript	c.4427C>T	p.Ser1476Leu	missense_variant	7/12		XP_006718788.1	Q9C0C2-1A0A024R542
TNKS1BP1	XM_047427785.1 linkuse as main transcript	c.2399C>T	p.Ser800Leu	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.4427C>T	p.Ser1476Leu	missense_variant	7/12	1	NM_033396.3	ENSP00000350990.3	Q9C0C2-1
TNKS1BP1	ENST00000532437.1 linkuse as main transcript	c.4427C>T	p.Ser1476Leu	missense_variant	6/11	1		ENSP00000437271.1	Q9C0C2-1
TNKS1BP1	ENST00000528882.5 linkuse as main transcript	n.*3103-2754C>T		intron_variant		5		ENSP00000431616.1	E9PKK0
TNKS1BP1	ENST00000427750.2 linkuse as main transcript	n.765C>T		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000760

AC:

AN:

1447268

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

719570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.2

DANN

Benign

0.38

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.013

Sift

Benign

0.61

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.054

B;B

Vest4

0.24

MVP

0.18

MPC

0.071

ClinPred

0.059

GERP RS

1.4

Varity_R

0.032

gMVP

0.097

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

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