Variant 8-9556169-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_003747.3(TNKS):c.230G>A(p.Arg77Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TNKS
NM_003747.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

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:

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=0.117795855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNKS	NM_003747.3 linkuse as main transcript	c.230G>A	p.Arg77Lys	missense_variant	1/27	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4 linkuse as main transcript	c.230G>A	p.Arg77Lys	missense_variant	1/28		XP_011542147.1
TNKS	XM_011543846.4 linkuse as main transcript	c.230G>A	p.Arg77Lys	missense_variant	1/27		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11 linkuse as main transcript	c.230G>A	p.Arg77Lys	missense_variant	1/27	1	NM_003747.3	ENSP00000311579	P1	O95271-1
TNKS	ENST00000517770.2 linkuse as main transcript	c.230G>A	p.Arg77Lys	missense_variant	1/28	4		ENSP00000428185
TNKS	ENST00000520408.5 linkuse as main transcript	c.230G>A	p.Arg77Lys	missense_variant	1/11	2		ENSP00000428299
TNKS	ENST00000522110.1 linkuse as main transcript	c.230G>A	p.Arg77Lys	missense_variant	1/1			ENSP00000430920

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248478

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459600

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725802

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Aug 13, 2021

The c.230G>A (p.R77K) alteration is located in exon 1 (coding exon 1) of the TNKS gene. This alteration results from a G to A substitution at nucleotide position 230, causing the arginine (R) at amino acid position 77 to be replaced by a lysine (K). 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

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

.;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

0.0039

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.69

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

.;N;.

MutationTaster

Benign

0.89

D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.13

N;N;N

REVEL

Benign

0.065

Sift

Benign

0.035

D;T;D

Sift4G

Benign

0.19

T;T;T

Polyphen

0.13

B;B;.

Vest4

0.31

MutPred

0.20

Gain of ubiquitination at R77 (P = 0.0022);Gain of ubiquitination at R77 (P = 0.0022);Gain of ubiquitination at R77 (P = 0.0022);

MVP

0.53

MPC

0.38

ClinPred

0.19

GERP RS

4.8

Varity_R

0.28

gMVP

0.12

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