rs5002814

Variant names:

• chr8-9609719-A-G
• rs5002814
• NM_003747.3:c.899-5863A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003747.3(TNKS):​c.899-5863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,090 control chromosomes in the GnomAD database, including 1,293 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 0.12 (1293 hom., cov: 32)
• Consequence: TNKS NM_003747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003747.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS	NM_003747.3	MANE Select	c.899-5863A>G		intron	N/A	NP_003738.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS	ENST00000310430.11	TSL:1 MANE Select	c.899-5863A>G		intron	N/A	ENSP00000311579.6
	TNKS	ENST00000517770.2	TSL:4	c.899-5863A>G		intron	N/A	ENSP00000428185.2
	TNKS	ENST00000518281.5	TSL:2	c.188-5863A>G		intron	N/A	ENSP00000429890.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18070 AN: 151974 Hom.: 1284 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.119 AC: 18114 AN: 152090 Hom.: 1293 Cov.: 32 AF XY: 0.120 AC XY: 8959 AN XY: 74356

African (AFR) AF: 0.207 AC: 8572 AN: 41452

American (AMR) AF: 0.113 AC: 1734 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.0951 AC: 492 AN: 5176

South Asian (SAS) AF: 0.182 AC: 879 AN: 4818

European-Finnish (FIN) AF: 0.0819 AC: 867 AN: 10580

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0747 AC: 5076 AN: 67986

Other (OTH) AF: 0.106 AC: 223 AN: 2104

Alfa AF: 0.102 Hom.: 130

Bravo AF: 0.123

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		1.1
Mutation Taster		=99/1	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: rs5002814; hg19: chr8-9467229;