rs11249943

Positions:

• chr8-9750353-A-C
• chr8-9750353-A-G

Variant summary

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

The NM_003747.3(TNKS):​c.2833-1256A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,126 control chromosomes in the GnomAD database, including 2,734 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 (2734 hom., cov: 32)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561

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=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS	NM_003747.3	c.2833-1256A>C		intron_variant		ENST00000310430.11
TNKS	XM_011543845.4	c.2833-1256A>C		intron_variant
TNKS	XM_011543846.4	c.2833-1256A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS	ENST00000310430.11	c.2833-1256A>C		intron_variant		1	NM_003747.3	P1
TNKS	ENST00000517770.2	c.2833-1256A>C		intron_variant		4
TNKS	ENST00000518281.5	c.2122-1256A>C		intron_variant		2
TNKS	ENST00000519191.1	n.392-1256A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27602 AN: 152008 Hom.: 2731 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.181 AC: 27610 AN: 152126 Hom.: 2734 Cov.: 32 AF XY: 0.184 AC XY: 13685 AN XY: 74370

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0980

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.153

Alfa AF: 0.178 Hom.: 4752

Bravo AF: 0.167

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.88

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: rs11249943; hg19: chr8-9607863;