Variant 8-9556141-G-T 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.202G>T(p.Gly68Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 5.71

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=0.21520284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS	NM_003747.3 link	c.202G>T	p.Gly68Trp	missense_variant	1/27	ENST00000310430.11	NP_003738.2	O95271-1
TNKS	XM_011543845.4 link	c.202G>T	p.Gly68Trp	missense_variant	1/28		XP_011542147.1
TNKS	XM_011543846.4 link	c.202G>T	p.Gly68Trp	missense_variant	1/27		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNKS	ENST00000310430.11 link	c.202G>T	p.Gly68Trp	missense_variant	1/27	1	NM_003747.3	ENSP00000311579.6	O95271-1
TNKS	ENST00000517770.2 link	c.202G>T	p.Gly68Trp	missense_variant	1/28	4		ENSP00000428185.2	H0YAW5
TNKS	ENST00000520408.5 link	c.202G>T	p.Gly68Trp	missense_variant	1/11	2		ENSP00000428299.1	E7EWY6
TNKS	ENST00000522110.1 link	c.202G>T	p.Gly68Trp	missense_variant	1/1	6		ENSP00000430920.1	E5RHD2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241712

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131514

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:

0.00000923

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

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

Nov 20, 2024

The c.202G>T (p.G68W) alteration is located in exon 1 (coding exon 1) of the TNKS gene. This alteration results from a G to T substitution at nucleotide position 202, causing the glycine (G) at amino acid position 68 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

0.25

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

.;T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.81

T;T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.69

.;N;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.22

N;N;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.99

D;P;.

Vest4

0.56

MutPred

0.15

Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);

MVP

0.31

MPC

0.44

ClinPred

0.76

GERP RS

4.8

Varity_R

0.13

gMVP

0.091

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