rs478699

Positions:

• chr9-76643479-T-C
• chr9-76643479-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015225.3(PRUNE2):​c.8728+1260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,066 control chromosomes in the GnomAD database, including 20,653 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 0.51 (20653 hom., cov: 33)
• Consequence: PRUNE2 NM_015225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.832

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]

LOC105376095 (HGNC:):

GCNT1 (HGNC:4203): (glucosaminyl (N-acetyl) transferase 1) This gene is a member of the beta-1,6-N-acetylglucosaminyltransferase gene family. It is essential to the formation of Gal beta 1-3(GlcNAc beta 1-6)GalNAc structures and the core 2 O-glycan branch. The gene coding this enzyme was originally mapped to 9q21, but was later localized to 9q13. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRUNE2	NM_015225.3	c.8728+1260A>G		intron_variant		ENST00000376718.8
LOC105376095	XR_007061586.1	n.1247+801T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRUNE2	ENST00000376718.8	c.8728+1260A>G		intron_variant		5	NM_015225.3	P1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76817 AN: 151950 Hom.: 20649 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.505 AC: 76851 AN: 152066 Hom.: 20653 Cov.: 33 AF XY: 0.507 AC XY: 37714 AN XY: 74328

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.552

Alfa AF: 0.552 Hom.: 5050

Bravo AF: 0.498

Asia WGS AF: 0.494 AC: 1716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs478699; hg19: chr9-79258395;