8-9715169-A-G

Variant names:

• chr8-9715169-A-G
• rs12155819
• NM_003747.3:c.1749+4949A>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.1749+4949A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,842 control chromosomes in the GnomAD database, including 26,290 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 0.58 (26290 hom., cov: 30)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.1749+4949A>G		intron_variant	Intron 11 of 26	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.1749+4949A>G		intron_variant	Intron 11 of 27		XP_011542147.1
TNKS	XM_011543846.4	c.1749+4949A>G		intron_variant	Intron 11 of 26		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.1749+4949A>G		intron_variant	Intron 11 of 26	1	NM_003747.3	ENSP00000311579.6
TNKS	ENST00000517770.2	c.1749+4949A>G		intron_variant	Intron 11 of 27	4		ENSP00000428185.2
TNKS	ENST00000518281.5	c.1038+4949A>G		intron_variant	Intron 11 of 26	2		ENSP00000429890.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88661 AN: 151724 Hom.: 26287 Cov.: 30

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.584 AC: 88688 AN: 151842 Hom.: 26290 Cov.: 30 AF XY: 0.579 AC XY: 42964 AN XY: 74198

African (AFR) AF: 0.519 AC: 21478 AN: 41382

American (AMR) AF: 0.554 AC: 8448 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2646 AN: 3468

East Asian (EAS) AF: 0.481 AC: 2475 AN: 5142

South Asian (SAS) AF: 0.564 AC: 2707 AN: 4798

European-Finnish (FIN) AF: 0.518 AC: 5468 AN: 10564

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43300 AN: 67920

Other (OTH) AF: 0.624 AC: 1317 AN: 2110

Alfa AF: 0.615 Hom.: 15583

Bravo AF: 0.580

Asia WGS AF: 0.511 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.73
PhyloP100		0.22
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: rs12155819; hg19: chr8-9572679;