8-9702659-A-G

Variant names:

• chr8-9702659-A-G
• rs9644704
• NM_003747.3:c.1108-2004A>G

Variant summary

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

The NM_003747.3(TNKS):​c.1108-2004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,078 control chromosomes in the GnomAD database, including 27,369 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 0.60 (27369 hom., cov: 33)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.1108-2004A>G		intron_variant	Intron 5 of 26	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.1108-2004A>G		intron_variant	Intron 5 of 27		XP_011542147.1
TNKS	XM_011543846.4	c.1108-2004A>G		intron_variant	Intron 5 of 26		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.1108-2004A>G		intron_variant	Intron 5 of 26	1	NM_003747.3	ENSP00000311579.6

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90595 AN: 151958 Hom.: 27366 Cov.: 33

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.596 AC: 90622 AN: 152078 Hom.: 27369 Cov.: 33 AF XY: 0.591 AC XY: 43912 AN XY: 74340

African (AFR) AF: 0.565 AC: 23435 AN: 41470

American (AMR) AF: 0.568 AC: 8687 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2635 AN: 3472

East Asian (EAS) AF: 0.398 AC: 2058 AN: 5170

South Asian (SAS) AF: 0.579 AC: 2793 AN: 4822

European-Finnish (FIN) AF: 0.514 AC: 5429 AN: 10554

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43387 AN: 67980

Other (OTH) AF: 0.637 AC: 1344 AN: 2110

Alfa AF: 0.618 Hom.: 13537

Bravo AF: 0.593

Asia WGS AF: 0.492 AC: 1711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		2.0
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: rs9644704; hg19: chr8-9560169;