NM_025235.4:c.1276-83G>T

Variant names:

• chr10-91833770-G-T
• rs1770474
• NM_025235.4:c.1276-83G>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.1276-83G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,115,968 control chromosomes in the GnomAD database, including 18,620 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 0.19 (2810 hom., cov: 33)
  • Exomes 𝑓: 0.18 (15810 hom.)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 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.1276-83G>T		intron	N/A	NP_079511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	ENST00000371627.5	TSL:1 MANE Select	c.1276-83G>T		intron	N/A	ENSP00000360689.4
	TNKS2	ENST00000710380.1		c.1315-83G>T		intron	N/A	ENSP00000518237.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28619 AN: 152034 Hom.: 2804 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.178 AC: 171737 AN: 963816 Hom.: 15810 AF XY: 0.179 AC XY: 84699 AN XY: 473880

African (AFR) AF: 0.221 AC: 4747 AN: 21528

American (AMR) AF: 0.103 AC: 1907 AN: 18534

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 3148 AN: 15008

East Asian (EAS) AF: 0.206 AC: 6549 AN: 31846

South Asian (SAS) AF: 0.176 AC: 5601 AN: 31838

European-Finnish (FIN) AF: 0.161 AC: 6074 AN: 37788

Middle Eastern (MID) AF: 0.238 AC: 830 AN: 3486

European-Non Finnish (NFE) AF: 0.177 AC: 135421 AN: 763354

Other (OTH) AF: 0.184 AC: 7460 AN: 40434

GnomAD4 genome AF: 0.188 AC: 28658 AN: 152152 Hom.: 2810 Cov.: 33 AF XY: 0.187 AC XY: 13887 AN XY: 74390

African (AFR) AF: 0.212 AC: 8782 AN: 41512

American (AMR) AF: 0.155 AC: 2361 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1127 AN: 5182

South Asian (SAS) AF: 0.175 AC: 845 AN: 4828

European-Finnish (FIN) AF: 0.162 AC: 1710 AN: 10582

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12350 AN: 67978

Other (OTH) AF: 0.200 AC: 422 AN: 2114

Alfa AF: 0.150 Hom.: 467

Bravo AF: 0.190

Asia WGS AF: 0.203 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.65
PhyloP100		1.4
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: rs1770474; hg19: chr10-93593527; COSMIC: COSV65415060;