rs1815282283

Variant names:

• chr8-9556145-A-G
• rs1815282283
• NM_003747.3:c.206A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003747.3(TNKS):​c.206A>G​(p.Asp69Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,607,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D69N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TNKS NM_003747.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

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]

ACMG classification

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=0.14710426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.206A>G	p.Asp69Gly	missense_variant	Exon 1 of 27	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.206A>G	p.Asp69Gly	missense_variant	Exon 1 of 28		XP_011542147.1
TNKS	XM_011543846.4	c.206A>G	p.Asp69Gly	missense_variant	Exon 1 of 27		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.206A>G	p.Asp69Gly	missense_variant	Exon 1 of 27	1	NM_003747.3	ENSP00000311579.6
TNKS	ENST00000517770.2	c.206A>G	p.Asp69Gly	missense_variant	Exon 1 of 28	4		ENSP00000428185.2
TNKS	ENST00000520408.5	c.206A>G	p.Asp69Gly	missense_variant	Exon 1 of 11	2		ENSP00000428299.1
TNKS	ENST00000522110.1	c.206A>G	p.Asp69Gly	missense_variant	Exon 1 of 1	6		ENSP00000430920.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455202 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 723140

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.0000450 AC: 2 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25700

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 85704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108570

Other (OTH) AF: 0.00 AC: 0 AN: 60086

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74300

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.206A>G (p.D69G) alteration is located in exon 1 (coding exon 1) of the TNKS gene. This alteration results from a A to G substitution at nucleotide position 206, causing the aspartic acid (D) at amino acid position 69 to be replaced by a glycine (G). 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	0.080
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	.;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.017
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.20	.;N;.
PhyloP100		2.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.090	N;N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D;D;D
Sift4G	Benign	0.79	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.34
MutPred		0.18		Gain of catalytic residue at D69 (P = 0.0516);Gain of catalytic residue at D69 (P = 0.0516);Gain of catalytic residue at D69 (P = 0.0516);
MVP		0.79
MPC		0.49
ClinPred		0.75	D
GERP RS		4.8
PromoterAI		-0.025	Neutral
Varity_R		0.23
gMVP		0.15
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1815282283; hg19: chr8-9413655;