Variant 9-76710039-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015225.3(PRUNE2):c.2235G>A(p.Met745Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,613,440 control chromosomes in the GnomAD database, including 23,925 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2830 hom., cov: 32)

Exomes 𝑓: 0.16 ( 21095 hom. )

Consequence

PRUNE2
NM_015225.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.406

Variant links:

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]

PRUNE2 links:

PRUNE2 (HGNC:):

PRUNE2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.009305E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRUNE2	NM_015225.3 linkuse as main transcript	c.2235G>A	p.Met745Ile	missense_variant	8/19	ENST00000376718.8	NP_056040.2	Q8WUY3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRUNE2	ENST00000376718.8 linkuse as main transcript	c.2235G>A	p.Met745Ile	missense_variant	8/19	5	NM_015225.3	ENSP00000365908.3		Q8WUY3-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27132

AN:

151918

Hom.:

2824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.483

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.186

AC:

46076

AN:

248090

Hom.:

5346

AF XY:

0.181

AC XY:

24412

AN XY:

134844

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.486

Gnomad SAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.156

AC:

227335

AN:

1461404

Hom.:

21095

Cov.:

AF XY:

0.156

AC XY:

113202

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.493

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.179

AC:

27153

AN:

152036

Hom.:

2830

Cov.:

AF XY:

0.187

AC XY:

13908

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.483

Gnomad4 SAS

AF:

0.187

Gnomad4 FIN

AF:

0.284

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.161

Alfa

AF:

0.151

Hom.:

3450

Bravo

AF:

0.173

TwinsUK

AF:

0.133

AC:

492

ALSPAC

AF:

0.128

AC:

493

ESP6500AA

AF:

0.200

AC:

627

ESP6500EA

AF:

0.123

AC:

882

ExAC

AF:

0.184

AC:

22175

Asia WGS

AF:

0.338

AC:

1177

AN:

3478

EpiCase

AF:

0.123

EpiControl

AF:

0.125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.056

DANN

Benign

0.45

DEOGEN2

Benign

0.0049

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.087

T;T;T

MetaRNN

Benign

0.00010

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.56

N;.;N

REVEL

Benign

0.060

Sift

Benign

0.45

T;.;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.059

MutPred

0.058

Loss of glycosylation at P744 (P = 0.1214);Loss of glycosylation at P744 (P = 0.1214);.;

MPC

0.092

ClinPred

0.0037

GERP RS

-0.97

Varity_R

0.060

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over