chr9-76643479-T-C

Variant names:

• chr9-76643479-T-C
• rs478699
• NM_015225.3:c.8728+1260A>G

Variant summary

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

The ENST00000376718.8(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 ENST00000376718.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.832
• Publications: 3 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]

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]

LOC105376095 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376718.8. 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
	PRUNE2	NM_015225.3	MANE Select	c.8728+1260A>G		intron	N/A	NP_056040.2
	PRUNE2	NM_001308048.2		c.8731+1260A>G		intron	N/A	NP_001294977.1
	PRUNE2	NM_001308047.2		c.8728+1260A>G		intron	N/A	NP_001294976.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRUNE2	ENST00000376718.8	TSL:5 MANE Select	c.8728+1260A>G		intron	N/A	ENSP00000365908.3
	PRUNE2	ENST00000443509.6	TSL:5	c.8728+1260A>G		intron	N/A	ENSP00000393843.3
	PRUNE2	ENST00000428286.5	TSL:5	c.7654+1260A>G		intron	N/A	ENSP00000397425.1

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

African (AFR) AF: 0.312 AC: 12933 AN: 41504

American (AMR) AF: 0.594 AC: 9079 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2283 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2381 AN: 5154

South Asian (SAS) AF: 0.629 AC: 3032 AN: 4820

European-Finnish (FIN) AF: 0.516 AC: 5448 AN: 10562

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 39996 AN: 67962

Other (OTH) AF: 0.552 AC: 1166 AN: 2114

Alfa AF: 0.548 Hom.: 8905

Bravo AF: 0.498

Asia WGS AF: 0.494 AC: 1716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.65
PhyloP100		0.83
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: rs478699; hg19: chr9-79258395;