10-91817384-T-G

Variant names:

• chr10-91817384-T-G
• rs1539041
• NM_025235.4:c.520+155T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025235.4(TNKS2):​c.520+155T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,220 control chromosomes in the GnomAD database, including 46,085 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 0.77 (46085 hom., cov: 33)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• Publications: 9 publications found

Genes affected

TNKS2 (HGNC:15677): (tankyrase 2) Enables NAD+ ADP-ribosyltransferase activity; enzyme binding activity; and protein ADP-ribosylase activity. Involved in several processes, including protein ADP-ribosylation; protein localization to chromosome, telomeric region; and regulation of telomere maintenance. Located in nuclear envelope; pericentriolar material; and perinuclear region of cytoplasm. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025235.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	NM_025235.4	MANE Select	c.520+155T>G		intron	N/A	NP_079511.1	Q9H2K2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	ENST00000371627.5	TSL:1 MANE Select	c.520+155T>G		intron	N/A	ENSP00000360689.4	Q9H2K2
	TNKS2	ENST00000710380.1		c.559+155T>G		intron	N/A	ENSP00000518237.1	A0AA34QVI1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117601 AN: 152102 Hom.: 46041 Cov.: 33

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.773 AC: 117703 AN: 152220 Hom.: 46085 Cov.: 33 AF XY: 0.782 AC XY: 58160 AN XY: 74418

African (AFR) AF: 0.856 AC: 35585 AN: 41558

American (AMR) AF: 0.770 AC: 11783 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2620 AN: 3468

East Asian (EAS) AF: 0.913 AC: 4725 AN: 5178

South Asian (SAS) AF: 0.878 AC: 4241 AN: 4830

European-Finnish (FIN) AF: 0.827 AC: 8746 AN: 10580

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47669 AN: 68000

Other (OTH) AF: 0.724 AC: 1527 AN: 2110

Alfa AF: 0.726 Hom.: 20409

Bravo AF: 0.769

Asia WGS AF: 0.891 AC: 3101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.69
PhyloP100		-0.52
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: rs1539041; hg19: chr10-93577141;