rs12412538

Variant names:

• chr10-91860119-A-T
• rs12412538
• NM_025235.4:c.3281+471A>T

Variant summary

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

The NM_025235.4(TNKS2):​c.3281+471A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,002 control chromosomes in the GnomAD database, including 8,600 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 0.33 (8600 hom., cov: 32)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 2 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]

ENSG00000302365 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.509 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	NM_025235.4	MANE Select	c.3281+471A>T		intron	N/A	NP_079511.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	ENST00000371627.5	TSL:1 MANE Select	c.3281+471A>T		intron	N/A	ENSP00000360689.4
	TNKS2	ENST00000710380.1		c.3320+471A>T		intron	N/A	ENSP00000518237.1
	ENSG00000302365	ENST00000786181.1		n.201+22909T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49549 AN: 151884 Hom.: 8595 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.326 AC: 49568 AN: 152002 Hom.: 8600 Cov.: 32 AF XY: 0.339 AC XY: 25157 AN XY: 74286

African (AFR) AF: 0.251 AC: 10392 AN: 41468

American (AMR) AF: 0.382 AC: 5839 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3470

East Asian (EAS) AF: 0.500 AC: 2584 AN: 5170

South Asian (SAS) AF: 0.526 AC: 2527 AN: 4806

European-Finnish (FIN) AF: 0.463 AC: 4884 AN: 10544

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21019 AN: 67958

Other (OTH) AF: 0.282 AC: 596 AN: 2112

Alfa AF: 0.317 Hom.: 974

Bravo AF: 0.309

Asia WGS AF: 0.491 AC: 1702 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.47
PhyloP100		0.24
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: rs12412538; hg19: chr10-93619876;