rs11787063

Variant names:

• chr8-9588790-G-T
• rs11787063
• NM_003747.3:c.898+8407G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003747.3(TNKS):​c.898+8407G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,164 control chromosomes in the GnomAD database, including 3,327 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (3327 hom., cov: 32)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.898+8407G>T		intron_variant	Intron 2 of 26	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.898+8407G>T		intron_variant	Intron 2 of 27		XP_011542147.1
TNKS	XM_011543846.4	c.898+8407G>T		intron_variant	Intron 2 of 26		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.898+8407G>T		intron_variant	Intron 2 of 26	1	NM_003747.3	ENSP00000311579.6
TNKS	ENST00000517770.2	c.898+8407G>T		intron_variant	Intron 2 of 27	4		ENSP00000428185.2
TNKS	ENST00000518281.5	c.187+8407G>T		intron_variant	Intron 2 of 26	2		ENSP00000429890.1
TNKS	ENST00000520408.5	c.898+8407G>T		intron_variant	Intron 2 of 10	2		ENSP00000428299.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27664 AN: 152046 Hom.: 3328 Cov.: 32

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0230

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.215

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27647 AN: 152164 Hom.: 3327 Cov.: 32 AF XY: 0.179 AC XY: 13298 AN XY: 74396

African (AFR) AF: 0.0451 AC: 1874 AN: 41534

American (AMR) AF: 0.159 AC: 2429 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1226 AN: 3468

East Asian (EAS) AF: 0.0230 AC: 119 AN: 5172

South Asian (SAS) AF: 0.102 AC: 492 AN: 4830

European-Finnish (FIN) AF: 0.246 AC: 2604 AN: 10572

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18229 AN: 67978

Other (OTH) AF: 0.212 AC: 447 AN: 2112

Alfa AF: 0.245 Hom.: 6205

Bravo AF: 0.166

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.79
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs11787063; hg19: chr8-9446300;