10-91862386-T-G

Variant names:

• chr10-91862386-T-G
• rs7087365
• NM_025235.4:c.3438+231T>G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS2	NM_025235.4	c.3438+231T>G		intron_variant	Intron 26 of 26	ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2	c.3501+231T>G		intron_variant	Intron 26 of 26		XP_011538515.1
TNKS2	XM_017016699.2	c.3117+231T>G		intron_variant	Intron 25 of 25		XP_016872188.1
TNKS2	XM_017016700.3	c.2142+231T>G		intron_variant	Intron 14 of 14		XP_016872189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5	c.3438+231T>G		intron_variant	Intron 26 of 26	1	NM_025235.4	ENSP00000360689.4
TNKS2	ENST00000710380.1	c.3477+231T>G		intron_variant	Intron 26 of 26			ENSP00000518237.1

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

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.283

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs7087365; hg19: chr10-93622143;