rs11249943

Variant names:

• chr8-9750353-A-C
• rs11249943
• NM_003747.3:c.2833-1256A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-9750353-A-C
• chr8-9750353-A-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.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
• Publications: 8 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=-0.65).
• 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 rank	MANE	Protein	UniProt
TNKS	NM_003747.3	c.2833-1256A>C		intron_variant	Intron 18 of 26	ENST00000310430.11	NP_003738.2
TNKS	XM_011543845.4	c.2833-1256A>C		intron_variant	Intron 18 of 27		XP_011542147.1
TNKS	XM_011543846.4	c.2833-1256A>C		intron_variant	Intron 18 of 26		XP_011542148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS	ENST00000310430.11	c.2833-1256A>C		intron_variant	Intron 18 of 26	1	NM_003747.3	ENSP00000311579.6
TNKS	ENST00000517770.2	c.2833-1256A>C		intron_variant	Intron 18 of 27	4		ENSP00000428185.2
TNKS	ENST00000518281.5	c.2122-1256A>C		intron_variant	Intron 18 of 26	2		ENSP00000429890.1
TNKS	ENST00000519191.1	n.392-1256A>C		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.159 AC: 6608 AN: 41508

American (AMR) AF: 0.128 AC: 1950 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.193 AC: 996 AN: 5170

South Asian (SAS) AF: 0.131 AC: 632 AN: 4818

European-Finnish (FIN) AF: 0.324 AC: 3425 AN: 10576

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13098 AN: 67984

Other (OTH) AF: 0.153 AC: 322 AN: 2110

Alfa AF: 0.182 Hom.: 10637

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
PhyloP100		0.56
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: rs11249943; hg19: chr8-9607863;