Variant 10-91798764-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_025235.4(TNKS2):c.74C>T(p.Ala25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000955 in 1,265,530 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

TNKS2
NM_025235.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

TNKS2 (HGNC:15677): (tankyrase 2) Enables NAD+ ADP-ribosyltransferase activity; enzyme binding activity; and protein ADP-ribosylase activity. Involved in several processes, including protein ADP-ribosylation; protein localization to chromosome, telomeric region; and regulation of telomere maintenance. Located in nuclear envelope; pericentriolar material; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TNKS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014120191).

BS2

High AC in GnomAd4 at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TNKS2	NM_025235.4 linkuse as main transcript	c.74C>T	p.Ala25Val	missense_variant	1/27	ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2 linkuse as main transcript	c.74C>T	p.Ala25Val	missense_variant	1/27		XP_011538515.1
TNKS2	XM_017016701.2 linkuse as main transcript	c.74C>T	p.Ala25Val	missense_variant	1/13		XP_016872190.1
TNKS2	XM_047425795.1 linkuse as main transcript	c.74C>T	p.Ala25Val	missense_variant	1/13		XP_047281751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5 linkuse as main transcript	c.74C>T	p.Ala25Val	missense_variant	1/27	1	NM_025235.4	ENSP00000360689	P1
TNKS2	ENST00000710380.1 linkuse as main transcript	c.113C>T	p.Ala38Val	missense_variant	1/27			ENSP00000518237

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000839

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000502

AC:

AN:

11956

Hom.:

AF XY:

0.000504

AC XY:

AN XY:

5948

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:

0.00200

Gnomad OTH exome

AF:

0.00556

GnomAD4 exome

AF:

0.00102

AC:

1139

AN:

1113344

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

541

AN XY:

529454

show subpopulations

Gnomad4 AFR exome

AF:

0.000172

Gnomad4 AMR exome

AF:

0.000452

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:

0.00117

Gnomad4 OTH exome

AF:

0.000920

GnomAD4 genome

AF:

0.000460

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000839

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000907

Hom.:

Bravo

AF:

0.000533

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000756

AC:

ExAC

AF:

0.000196

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

Apr 21, 2022

The c.74C>T (p.A25V) alteration is located in exon 1 (coding exon 1) of the TNKS2 gene. This alteration results from a C to T substitution at nucleotide position 74, causing the alanine (A) at amino acid position 25 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

0.14

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

0.019

Eigen_PC

Benign

0.095

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.93

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.020

REVEL

Benign

0.10

Sift

Benign

0.61

Sift4G

Benign

0.54

Polyphen

0.67

Vest4

0.28

MVP

0.49

MPC

1.6

ClinPred

0.13

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.15

gMVP

0.23

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