Variant chr10-91798761-C-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_025235.4(TNKS2):c.71C>T(p.Ala24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNKS2
NM_025235.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

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:

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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=0.17975387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNKS2	NM_025235.4 linkuse as main transcript	c.71C>T	p.Ala24Val	missense_variant	1/27	ENST00000371627.5
TNKS2	XM_011540213.2 linkuse as main transcript	c.71C>T	p.Ala24Val	missense_variant	1/27
TNKS2	XM_017016701.2 linkuse as main transcript	c.71C>T	p.Ala24Val	missense_variant	1/13
TNKS2	XM_047425795.1 linkuse as main transcript	c.71C>T	p.Ala24Val	missense_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5 linkuse as main transcript	c.71C>T	p.Ala24Val	missense_variant	1/27	1	NM_025235.4	P1
TNKS2	ENST00000710380.1 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	1/27

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1101726

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

522172

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:

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

Sep 29, 2023

The c.71C>T (p.A24V) 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 71, causing the alanine (A) at amino acid position 24 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

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Benign

-0.064

Eigen_PC

Benign

-0.029

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

MutationTaster

Benign

0.95

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.17

REVEL

Benign

0.059

Sift

Benign

0.27

Sift4G

Benign

0.33

Polyphen

0.80

Vest4

0.070

MutPred

0.21

Loss of loop (P = 0.1258);

MVP

0.44

MPC

1.6

ClinPred

0.47

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.042

gMVP

0.19

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over