rs6990300

Positions:

• chr8-9690351-G-A
• chr8-9690351-G-C

Variant summary

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

The NM_003747.3(TNKS):​c.1107+9551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,108 control chromosomes in the GnomAD database, including 29,677 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 0.62 (29677 hom., cov: 33)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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 = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS	NM_003747.3	c.1107+9551G>A		intron_variant		ENST00000310430.11
TNKS	XM_011543845.4	c.1107+9551G>A		intron_variant
TNKS	XM_011543846.4	c.1107+9551G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS	ENST00000310430.11	c.1107+9551G>A		intron_variant		1	NM_003747.3	P1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94320 AN: 151988 Hom.: 29678 Cov.: 33

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.620 AC: 94343 AN: 152108 Hom.: 29677 Cov.: 33 AF XY: 0.614 AC XY: 45623 AN XY: 74334

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.659

Alfa AF: 0.647 Hom.: 12769

Bravo AF: 0.617

Asia WGS AF: 0.515 AC: 1791 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	2.1
DANN	Benign	0.70

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: rs6990300; hg19: chr8-9547861;