8-9744189-G-T

Position:

• chr8-9744189-G-T

Variant summary

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

The NM_003747.3(TNKS):​c.2644-3835G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,014 control chromosomes in the GnomAD database, including 39,977 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 0.72 (39977 hom., cov: 32)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS	NM_003747.3	c.2644-3835G>T		intron_variant		ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.2644-3835G>T		intron_variant			XP_011542147.1
TNKS	XM_011543846.4	c.2644-3835G>T		intron_variant			XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.2644-3835G>T		intron_variant		1	NM_003747.3	ENSP00000311579	P1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109812 AN: 151896 Hom.: 39961 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.723 AC: 109862 AN: 152014 Hom.: 39977 Cov.: 32 AF XY: 0.719 AC XY: 53426 AN XY: 74284

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.763

Alfa AF: 0.755 Hom.: 87582

Bravo AF: 0.735

Asia WGS AF: 0.692 AC: 2399 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.67

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: rs12545912; hg19: chr8-9601699;