chr8-9556117-C-T

Variant names:

• chr8-9556117-C-T
• rs778919240
• NM_003747.3:c.178C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003747.3(TNKS):​c.178C>T​(p.Arg60Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R60G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNKS NM_003747.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29987848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.178C>T	p.Arg60Trp	missense_variant	Exon 1 of 27	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.178C>T	p.Arg60Trp	missense_variant	Exon 1 of 28		XP_011542147.1
TNKS	XM_011543846.4	c.178C>T	p.Arg60Trp	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.178C>T	p.Arg60Trp	missense_variant	Exon 1 of 27	1	NM_003747.3	ENSP00000311579.6
TNKS	ENST00000517770.2	c.178C>T	p.Arg60Trp	missense_variant	Exon 1 of 28	4		ENSP00000428185.2
TNKS	ENST00000520408.5	c.178C>T	p.Arg60Trp	missense_variant	Exon 1 of 11	2		ENSP00000428299.1
TNKS	ENST00000522110.1	c.178C>T	p.Arg60Trp	missense_variant	Exon 1 of 1	6		ENSP00000430920.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000436 AC: 1 AN: 229566 AF XY: 0.00000796

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000974

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1448706 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719560

African (AFR) AF: 0.00 AC: 0 AN: 33232

American (AMR) AF: 0.00 AC: 0 AN: 43820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39506

South Asian (SAS) AF: 0.00 AC: 0 AN: 84642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106252

Other (OTH) AF: 0.00 AC: 0 AN: 59752

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.55	.;N;.
PhyloP100		0.99
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.23	N;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.47
MutPred		0.22		Loss of phosphorylation at S58 (P = 0.1035);Loss of phosphorylation at S58 (P = 0.1035);Loss of phosphorylation at S58 (P = 0.1035);
MVP		0.59
MPC		0.39
ClinPred		0.82	D
GERP RS		0.75
PromoterAI		-0.066	Neutral
Varity_R		0.19
gMVP		0.18
Mutation Taster		=94/6	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: rs778919240; hg19: chr8-9413627;