rs12549064

Positions:

• chr8-9584517-A-C
• chr8-9584517-A-G
• chr8-9584517-A-T

Variant summary

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

The ENST00000310430.11(TNKS):​c.898+4134A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,948 control chromosomes in the GnomAD database, including 2,598 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 0.18 (2598 hom., cov: 32)
• Consequence: TNKS ENST00000310430.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS	NM_003747.3	c.898+4134A>C		intron_variant		ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.898+4134A>C		intron_variant			XP_011542147.1
TNKS	XM_011543846.4	c.898+4134A>C		intron_variant			XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.898+4134A>C		intron_variant		1	NM_003747.3	ENSP00000311579	P1
TNKS	ENST00000517770.2	c.898+4134A>C		intron_variant		4		ENSP00000428185
TNKS	ENST00000518281.5	c.187+4134A>C		intron_variant		2		ENSP00000429890
TNKS	ENST00000520408.5	c.898+4134A>C		intron_variant		2		ENSP00000428299

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26867 AN: 151830 Hom.: 2595 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0889

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.177 AC: 26886 AN: 151948 Hom.: 2598 Cov.: 32 AF XY: 0.179 AC XY: 13294 AN XY: 74242

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0889

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.146

Alfa AF: 0.159 Hom.: 2603

Bravo AF: 0.167

Asia WGS AF: 0.203 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.44

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: rs12549064; hg19: chr8-9442027;