Genetic Variant TNKS:p.Gly23Arg (chr8-9556006-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003747.3(TNKS):c.67G>A(p.Gly23Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,820 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TNKS
NM_003747.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.74

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26995632).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003747.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS	NM_003747.3	MANE Select	c.67G>A	p.Gly23Arg	missense	Exon 1 of 27	NP_003738.2	O95271-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNKS	ENST00000310430.11	TSL:1 MANE Select	c.67G>A	p.Gly23Arg	missense	Exon 1 of 27	ENSP00000311579.6	O95271-1
TNKS	ENST00000517770.2	TSL:4	c.67G>A	p.Gly23Arg	missense	Exon 1 of 28	ENSP00000428185.2	H0YAW5
TNKS	ENST00000885812.1		c.67G>A	p.Gly23Arg	missense	Exon 1 of 27	ENSP00000555871.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460820

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52798

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111820

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.46

MutationAssessor

Benign

0.0

PhyloP100

4.7

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.29

REVEL

Benign

0.13

Sift

Benign

0.035

Sift4G

Benign

0.16

Polyphen

0.98

Vest4

0.47

MutPred

0.24

Gain of solvent accessibility (P = 0.0097)

MVP

0.44

MPC

0.45

ClinPred

0.82

GERP RS

4.7

PromoterAI

0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.081

Mutation Taster

=89/11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over