NM_015225.3:c.9083A>G

Variant names:

• chr9-76629258-T-C
• rs180939665
• NM_015225.3:c.9083A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_015225.3(PRUNE2):​c.9083A>G​(p.Asn3028Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000948 in 1,593,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: PRUNE2 NM_015225.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0130
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00681144).
• BP6: Variant 9-76629258-T-C is Benign according to our data. Variant chr9-76629258-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2590375.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015225.3. 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
	PRUNE2	NM_015225.3	MANE Select	c.9083A>G	p.Asn3028Ser	missense	Exon 16 of 19	NP_056040.2	Q8WUY3-1
	PRUNE2	NM_001308048.2		c.9095A>G	p.Asn3032Ser	missense	Exon 17 of 18	NP_001294977.1
	PRUNE2	NM_001308047.2		c.9092A>G	p.Asn3031Ser	missense	Exon 17 of 18	NP_001294976.1	A0A088AWP5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRUNE2	ENST00000376718.8	TSL:5 MANE Select	c.9083A>G	p.Asn3028Ser	missense	Exon 16 of 19	ENSP00000365908.3	Q8WUY3-1
	PRUNE2	ENST00000443509.6	TSL:5	c.9092A>G	p.Asn3031Ser	missense	Exon 17 of 18	ENSP00000393843.3	A0A088AWP5
	PRUNE2	ENST00000428286.5	TSL:5	c.8009A>G	p.Asn2670Ser	missense	Exon 16 of 19	ENSP00000397425.1	E9PDC2

Frequencies

GnomAD3 genomes AF: 0.000468 AC: 71 AN: 151818 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000948

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000141 AC: 32 AN: 227634 AF XY: 0.000130

Gnomad AFR exome AF: 0.00146

Gnomad AMR exome AF: 0.0000315

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000285

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000555 AC: 80 AN: 1441562 Hom.: 0 Cov.: 27 AF XY: 0.0000516 AC XY: 37 AN XY: 716758

African (AFR) AF: 0.00134 AC: 44 AN: 32828

American (AMR) AF: 0.0000700 AC: 3 AN: 42830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25754

East Asian (EAS) AF: 0.00 AC: 0 AN: 39480

South Asian (SAS) AF: 0.000230 AC: 19 AN: 82640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49300

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5710

European-Non Finnish (NFE) AF: 0.00000906 AC: 10 AN: 1103292

Other (OTH) AF: 0.0000502 AC: 3 AN: 59728

GnomAD4 genome AF: 0.000467 AC: 71 AN: 151934 Hom.: 0 Cov.: 32 AF XY: 0.000444 AC XY: 33 AN XY: 74272

African (AFR) AF: 0.00159 AC: 66 AN: 41414

American (AMR) AF: 0.0000655 AC: 1 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.0000948 AC: 1 AN: 10546

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67956

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000191 Hom.: 0

Bravo AF: 0.000476

ESP6500AA AF: 0.00159 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000183 AC: 22

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.62
DANN	Benign	0.39
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.45	N
PhyloP100		-0.013
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.011
Sift	Benign	0.87	T
Sift4G	Benign	1.0	T
Polyphen		0.021	B
Vest4		0.088
MVP		0.24
MPC		0.068
ClinPred		0.00081	T
GERP RS		-1.5
Varity_R		0.021
gMVP		0.22
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs180939665; hg19: chr9-79244174;