rs7015700

Positions:

• chr8-9670197-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003747.3(TNKS):​c.995-9754G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,128 control chromosomes in the GnomAD database, including 4,620 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 0.24 (4620 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS	NM_003747.3	c.995-9754G>A		intron_variant		ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.995-9754G>A		intron_variant			XP_011542147.1
TNKS	XM_011543846.4	c.995-9754G>A		intron_variant			XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.995-9754G>A		intron_variant		1	NM_003747.3	ENSP00000311579	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35689 AN: 152010 Hom.: 4599 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.224

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.235 AC: 35758 AN: 152128 Hom.: 4620 Cov.: 32 AF XY: 0.238 AC XY: 17716 AN XY: 74374

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.230

Alfa AF: 0.198 Hom.: 4901

Bravo AF: 0.249

Asia WGS AF: 0.328 AC: 1139 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.069
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs7015700; hg19: chr8-9527707;