8-9744189-G-T

Variant names:

• chr8-9744189-G-T
• rs12545912
• NM_003747.3:c.2644-3835G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.81).
• 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 rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.2644-3835G>T		intron_variant	Intron 17 of 26	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.2644-3835G>T		intron_variant	Intron 17 of 27		XP_011542147.1
TNKS	XM_011543846.4	c.2644-3835G>T		intron_variant	Intron 17 of 26		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.2644-3835G>T		intron_variant	Intron 17 of 26	1	NM_003747.3	ENSP00000311579.6

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

African (AFR) AF: 0.656 AC: 27183 AN: 41444

American (AMR) AF: 0.808 AC: 12351 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2954 AN: 3468

East Asian (EAS) AF: 0.730 AC: 3778 AN: 5176

South Asian (SAS) AF: 0.701 AC: 3379 AN: 4820

European-Finnish (FIN) AF: 0.621 AC: 6536 AN: 10528

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51126 AN: 67974

Other (OTH) AF: 0.763 AC: 1614 AN: 2114

Alfa AF: 0.749 Hom.: 139968

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
PhyloP100		1.0
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: rs12545912; hg19: chr8-9601699;