rs2129048181

Variant names:

Variant summary

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

The NM_003747.3(TNKS):c.121C>T(p.Pro41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P41L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TNKS
NM_003747.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.116

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:

Genome browser will be placed here

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=0.13273242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3 link	c.121C>T	p.Pro41Ser	missense_variant	Exon 1 of 27	ENST00000310430.11	NP_003738.2	O95271-1
TNKS	XM_011543845.4 link	c.121C>T	p.Pro41Ser	missense_variant	Exon 1 of 28		XP_011542147.1
TNKS	XM_011543846.4 link	c.121C>T	p.Pro41Ser	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.121C>T	p.Pro41Ser	missense_variant	Exon 1 of 27	1	NM_003747.3	ENSP00000311579.6	O95271-1
TNKS	ENST00000517770.2 link	c.121C>T	p.Pro41Ser	missense_variant	Exon 1 of 28	4		ENSP00000428185.2	H0YAW5
TNKS	ENST00000520408.5 link	c.121C>T	p.Pro41Ser	missense_variant	Exon 1 of 11	2		ENSP00000428299.1	E7EWY6
TNKS	ENST00000522110.1 link	c.121C>T	p.Pro41Ser	missense_variant	Exon 1 of 1	6		ENSP00000430920.1	E5RHD2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456438

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.00

AC:

AN:

44384

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25884

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

85960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110426

Other (OTH)

AF:

0.00

AC:

AN:

60090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Mar 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.121C>T (p.P41S) alteration is located in exon 1 (coding exon 1) of the TNKS gene. This alteration results from a C to T substitution at nucleotide position 121, causing the proline (P) at amino acid position 41 to be replaced by a serine (S). 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

0.071

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.66

T;T;T

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

.;N;.

PhyloP100

0.12

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.13

N;N;N

REVEL

Benign

0.040

Sift

Benign

0.043

D;D;D

Sift4G

Benign

0.25

T;T;T

Polyphen

0.27

B;B;.

Vest4

0.23

MutPred

0.16

Gain of phosphorylation at P41 (P = 0.0172);Gain of phosphorylation at P41 (P = 0.0172);Gain of phosphorylation at P41 (P = 0.0172);

MVP

0.20

MPC

0.38

ClinPred

0.20

GERP RS

4.0

PromoterAI

0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.093

gMVP

0.12

Mutation Taster

=92/8

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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rs2129048181

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over