Variant 8-9556105-T-G 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_003747.3(TNKS):c.166T>G(p.Phe56Val) 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 1,448,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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

TNKS
NM_003747.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.988

Variant links:

Genes affected

TNKS (HGNC:11941): (tankyrase) Enables histone binding activity; pentosyltransferase activity; and zinc ion binding activity. Involved in several processes, including negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric; protein ADP-ribosylation; and regulation of nucleobase-containing compound metabolic process. Acts upstream of or within peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; and protein ADP-ribosylation. Located in several cellular components, including chromosome, telomeric region; mitotic spindle pole; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TNKS 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=0.09090543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNKS	NM_003747.3 linkuse as main transcript	c.166T>G	p.Phe56Val	missense_variant	1/27	ENST00000310430.11
TNKS	XM_011543845.4 linkuse as main transcript	c.166T>G	p.Phe56Val	missense_variant	1/28
TNKS	XM_011543846.4 linkuse as main transcript	c.166T>G	p.Phe56Val	missense_variant	1/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS	ENST00000310430.11 linkuse as main transcript	c.166T>G	p.Phe56Val	missense_variant	1/27	1	NM_003747.3	P1	O95271-1
TNKS	ENST00000517770.2 linkuse as main transcript	c.166T>G	p.Phe56Val	missense_variant	1/28	4
TNKS	ENST00000520408.5 linkuse as main transcript	c.166T>G	p.Phe56Val	missense_variant	1/11	2
TNKS	ENST00000522110.1 linkuse as main transcript	c.166T>G	p.Phe56Val	missense_variant	1/1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000438

AC:

AN:

228420

Hom.:

AF XY:

0.00000799

AC XY:

AN XY:

125140

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:

0.0000349

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1448676

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719604

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:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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 29, 2022

The c.166T>G (p.F56V) alteration is located in exon 1 (coding exon 1) of the TNKS gene. This alteration results from a T to G substitution at nucleotide position 166, causing the phenylalanine (F) at amino acid position 56 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.29

.;T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.74

T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.091

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.098

Sift

Benign

0.056

T;T;D

Sift4G

Benign

0.60

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.42

MutPred

0.18

Gain of glycosylation at S58 (P = 0.1583);Gain of glycosylation at S58 (P = 0.1583);Gain of glycosylation at S58 (P = 0.1583);

MVP

0.23

MPC

0.49

ClinPred

0.20

GERP RS

4.8

Varity_R

0.18

gMVP

0.068

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