Genetic Variant TNKS:p.Pro20Arg (chr8-9555998-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003747.3(TNKS):c.59C>G(p.Pro20Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P20A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TNKS
NM_003747.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.58

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17577419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3 link	c.59C>G	p.Pro20Arg	missense_variant	Exon 1 of 27	ENST00000310430.11	NP_003738.2	O95271-1
TNKS	XM_011543845.4 link	c.59C>G	p.Pro20Arg	missense_variant	Exon 1 of 28		XP_011542147.1
TNKS	XM_011543846.4 link	c.59C>G	p.Pro20Arg	missense_variant	Exon 1 of 27		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNKS	ENST00000310430.11 link	c.59C>G	p.Pro20Arg	missense_variant	Exon 1 of 27	1	NM_003747.3	ENSP00000311579.6	O95271-1
TNKS	ENST00000517770.2 link	c.59C>G	p.Pro20Arg	missense_variant	Exon 1 of 28	4		ENSP00000428185.2	H0YAW5
TNKS	ENST00000520408.5 link	c.59C>G	p.Pro20Arg	missense_variant	Exon 1 of 11	2		ENSP00000428299.1	E7EWY6
TNKS	ENST00000522110.1 link	c.59C>G	p.Pro20Arg	missense_variant	Exon 1 of 1	6		ENSP00000430920.1	E5RHD2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461064

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726838

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111854

Other (OTH)

AF:

0.00

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

.;T;.

Eigen

Benign

0.088

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.084

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

.;N;.

PhyloP100

5.6

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.080

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.049

D;D;D

Polyphen

0.39

B;P;.

Vest4

0.44

MutPred

0.26

Gain of MoRF binding (P = 0.0106);Gain of MoRF binding (P = 0.0106);Gain of MoRF binding (P = 0.0106);

MVP

0.37

MPC

0.39

ClinPred

0.57

GERP RS

4.8

PromoterAI

-0.045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.13

Mutation Taster

=63/37

polymorphism

(source)

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

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8-9555998-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over