8-9556040-C-G

Variant names:

• chr8-9556040-C-G
• rs371322654
• NM_003747.3:c.101C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_003747.3(TNKS):​c.101C>G​(p.Pro34Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,611,564 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. P34Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: TNKS NM_003747.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2586866).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.101C>G	p.Pro34Arg	missense_variant	Exon 1 of 27	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.101C>G	p.Pro34Arg	missense_variant	Exon 1 of 28		XP_011542147.1
TNKS	XM_011543846.4	c.101C>G	p.Pro34Arg	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.101C>G	p.Pro34Arg	missense_variant	Exon 1 of 27	1	NM_003747.3	ENSP00000311579.6
TNKS	ENST00000517770.2	c.101C>G	p.Pro34Arg	missense_variant	Exon 1 of 28	4		ENSP00000428185.2
TNKS	ENST00000520408.5	c.101C>G	p.Pro34Arg	missense_variant	Exon 1 of 11	2		ENSP00000428299.1
TNKS	ENST00000522110.1	c.101C>G	p.Pro34Arg	missense_variant	Exon 1 of 1	6		ENSP00000430920.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1459344 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 725998

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111432

Other (OTH) AF: 0.00 AC: 0 AN: 60258

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74356

African (AFR) AF: 0.0000482 AC: 2 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15290

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: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	.;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.0	.;N;.
PhyloP100		4.5
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.19	N;N;N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.098	T;T;D
Polyphen		0.91	P;B;.
Vest4		0.52
MutPred		0.25		Loss of glycosylation at P34 (P = 6e-04);Loss of glycosylation at P34 (P = 6e-04);Loss of glycosylation at P34 (P = 6e-04);
MVP		0.24
MPC		0.39
ClinPred		0.67	D
GERP RS		4.8
PromoterAI		0.064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.43
gMVP		0.096
Mutation Taster		=83/17	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: rs371322654; hg19: chr8-9413550;