chr10-91862386-T-G

Variant names:

• chr10-91862386-T-G
• rs7087365
• NM_025235.4:c.3438+231T>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.3438+231T>G 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 152,040 control chromosomes in the GnomAD database, including 8,622 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 (8622 hom., cov: 32)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.511 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.3438+231T>G		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.3438+231T>G		intron	N/A	ENSP00000360689.4
	TNKS2	ENST00000710380.1		c.3477+231T>G		intron	N/A	ENSP00000518237.1
	ENSG00000302365	ENST00000786181.1		n.201+20642A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49595 AN: 151922 Hom.: 8617 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.464

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: 49614 AN: 152040 Hom.: 8622 Cov.: 32 AF XY: 0.339 AC XY: 25174 AN XY: 74304

African (AFR) AF: 0.250 AC: 10387 AN: 41476

American (AMR) AF: 0.384 AC: 5866 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3468

East Asian (EAS) AF: 0.498 AC: 2568 AN: 5158

South Asian (SAS) AF: 0.528 AC: 2544 AN: 4820

European-Finnish (FIN) AF: 0.464 AC: 4891 AN: 10550

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

European-Non Finnish (NFE) AF: 0.309 AC: 21020 AN: 67968

Other (OTH) AF: 0.283 AC: 597 AN: 2112

Alfa AF: 0.317 Hom.: 978

Bravo AF: 0.310

Asia WGS AF: 0.494 AC: 1711 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs7087365; hg19: chr10-93622143;