Variant 11-57302710-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_033396.3(TNKS1BP1):c.4432C>T(p.Leu1478Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TNKS1BP1
NM_033396.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1270293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNKS1BP1	NM_033396.3 linkuse as main transcript	c.4432C>T	p.Leu1478Phe	missense_variant	7/12	ENST00000358252.8	NP_203754.2
TNKS1BP1	XM_006718725.4 linkuse as main transcript	c.4432C>T	p.Leu1478Phe	missense_variant	7/12		XP_006718788.1
TNKS1BP1	XM_047427785.1 linkuse as main transcript	c.2404C>T	p.Leu802Phe	missense_variant	3/8		XP_047283741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS1BP1	ENST00000358252.8 linkuse as main transcript	c.4432C>T	p.Leu1478Phe	missense_variant	7/12	1	NM_033396.3	ENSP00000350990	P1	Q9C0C2-1
TNKS1BP1	ENST00000532437.1 linkuse as main transcript	c.4432C>T	p.Leu1478Phe	missense_variant	6/11	1		ENSP00000437271	P1	Q9C0C2-1
TNKS1BP1	ENST00000427750.2 linkuse as main transcript	n.770C>T		non_coding_transcript_exon_variant	1/6	2
TNKS1BP1	ENST00000528882.5 linkuse as main transcript	c.*3103-2749C>T		intron_variant, NMD_transcript_variant		5		ENSP00000431616

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000876

AC:

AN:

228312

Hom.:

AF XY:

0.00000800

AC XY:

AN XY:

124964

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000192

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1448976

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720510

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 26, 2024

The c.4432C>T (p.L1478F) 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 4432, causing the leucine (L) at amino acid position 1478 to be replaced by a phenylalanine (F). 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

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.0089

T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.72

.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.053

Sift

Benign

0.22

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.90

P;P

Vest4

0.15

MutPred

0.11

Loss of MoRF binding (P = 0.1269);Loss of MoRF binding (P = 0.1269);

MVP

0.39

MPC

0.33

ClinPred

0.13

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.040

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