9-76891638-C-A

Variant names:

• chr9-76891638-C-A
• rs10512058
• NM_015225.3:c.36+14290G>T

Variant summary

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

The NM_015225.3(PRUNE2):​c.36+14290G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,280 control chromosomes in the GnomAD database, including 1,168 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 0.11 (1168 hom., cov: 33)
• Consequence: PRUNE2 NM_015225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 1 publications found

Genes affected

PRUNE2 (HGNC:25209): (prune homolog 2 with BCH domain) The protein encoded by this gene belongs to the B-cell CLL/lymphoma 2 and adenovirus E1B 19 kDa interacting family, whose members play roles in many cellular processes including apotosis, cell transformation, and synaptic function. Several functions for this protein have been demonstrated including suppression of Ras homolog family member A activity, which results in reduced stress fiber formation and suppression of oncogenic cellular transformation. A high molecular weight isoform of this protein has also been shown to colocalize with Adaptor protein complex 2, beta-Adaptin and endodermal markers, suggesting an involvement in post-endocytic trafficking. In prostate cancer cells, this gene acts as a tumor suppressor and its expression is regulated by prostate cancer antigen 3, a non-protein coding gene on the opposite DNA strand in an intron of this gene. Prostate cancer antigen 3 regulates levels of this gene through formation of a double-stranded RNA that undergoes adenosine deaminase actin on RNA-dependent adenosine-to-inosine RNA editing. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRUNE2	NM_015225.3	c.36+14290G>T		intron_variant	Intron 1 of 18	ENST00000376718.8	NP_056040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRUNE2	ENST00000376718.8	c.36+14290G>T		intron_variant	Intron 1 of 18	5	NM_015225.3	ENSP00000365908.3

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16538 AN: 152162 Hom.: 1166 Cov.: 33

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.109 AC: 16547 AN: 152280 Hom.: 1168 Cov.: 33 AF XY: 0.112 AC XY: 8375 AN XY: 74454

African (AFR) AF: 0.0401 AC: 1668 AN: 41574

American (AMR) AF: 0.122 AC: 1869 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 491 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1268 AN: 5172

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4820

European-Finnish (FIN) AF: 0.145 AC: 1541 AN: 10608

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8264 AN: 68014

Other (OTH) AF: 0.109 AC: 230 AN: 2114

Alfa AF: 0.114 Hom.: 144

Bravo AF: 0.105

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.82
DANN	Benign	0.70
PhyloP100		-0.44
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: rs10512058; hg19: chr9-79506554;