8-9679917-A-G

Position:

• chr8-9679917-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003747.3(TNKS):​c.995-34A>G variant causes a intron change. The variant allele was found at a frequency of 0.0868 in 1,586,392 control chromosomes in the GnomAD database, including 6,874 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 0.097 (788 hom., cov: 32)
  • Exomes 𝑓: 0.086 (6086 hom.)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS	NM_003747.3	c.995-34A>G		intron_variant		ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.995-34A>G		intron_variant			XP_011542147.1
TNKS	XM_011543846.4	c.995-34A>G		intron_variant			XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.995-34A>G		intron_variant		1	NM_003747.3	ENSP00000311579	P1

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14785 AN: 152048 Hom.: 782 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0963

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.0804

GnomAD3 exomes AF: 0.0995 AC: 24842 AN: 249628 Hom.: 1366 AF XY: 0.104 AC XY: 14090 AN XY: 135052

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.0860

Gnomad ASJ exome AF: 0.0605

Gnomad EAS exome AF: 0.0952

Gnomad SAS exome AF: 0.188

Gnomad FIN exome AF: 0.0950

Gnomad NFE exome AF: 0.0817

Gnomad OTH exome AF: 0.0843

GnomAD4 exome AF: 0.0857 AC: 122904 AN: 1434226 Hom.: 6086 Cov.: 26 AF XY: 0.0888 AC XY: 63527 AN XY: 715064

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.0855

Gnomad4 ASJ exome AF: 0.0615

Gnomad4 EAS exome AF: 0.0986

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.0954

Gnomad4 NFE exome AF: 0.0766

Gnomad4 OTH exome AF: 0.0858

GnomAD4 genome AF: 0.0974 AC: 14816 AN: 152166 Hom.: 788 Cov.: 32 AF XY: 0.100 AC XY: 7456 AN XY: 74382

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0950

Gnomad4 ASJ AF: 0.0556

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.0963

Gnomad4 NFE AF: 0.0803

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.0857 Hom.: 590

Bravo AF: 0.0961

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs6985140; hg19: chr8-9537427; COSMIC: COSV60058316;