8-9702659-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.78).
• 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/exons	MANE	UniProt
TNKS	NM_003747.3	c.1108-2004A>G		intron_variant		ENST00000310430.11
TNKS	XM_011543845.4	c.1108-2004A>G		intron_variant
TNKS	XM_011543846.4	c.1108-2004A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS	ENST00000310430.11	c.1108-2004A>G		intron_variant		1	NM_003747.3	P1

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

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.637

Alfa AF: 0.615 Hom.: 11813

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

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: rs9644704; hg19: chr8-9560169;