Variant chr9-76707152-G-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.5122C>A(p.His1708Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,613,426 control chromosomes in the GnomAD database, including 281,638 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 0.54 ( 23291 hom., cov: 31)

Exomes 𝑓: 0.59 ( 258347 hom. )

Consequence

PRUNE2
NM_015225.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

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=5.676775E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.639 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.5122C>A	p.His1708Asn	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.5122C>A	p.His1708Asn	missense_variant	8/19	5	NM_015225.3	ENSP00000365908.3		Q8WUY3-1

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82585

AN:

151792

Hom.:

23276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.651

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.571

Gnomad FIN

AF:

0.520

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.611

GnomAD3 exomes

AF:

0.590

AC:

146485

AN:

248234

Hom.:

44280

AF XY:

0.594

AC XY:

80069

AN XY:

134844

show subpopulations

Gnomad AFR exome

AF:

0.392

Gnomad AMR exome

AF:

0.702

Gnomad ASJ exome

AF:

0.711

Gnomad EAS exome

AF:

0.452

Gnomad SAS exome

AF:

0.581

Gnomad FIN exome

AF:

0.515

Gnomad NFE exome

AF:

0.610

Gnomad OTH exome

AF:

0.615

GnomAD4 exome

AF:

0.592

AC:

865367

AN:

1461516

Hom.:

258347

Cov.:

AF XY:

0.593

AC XY:

431281

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.393

Gnomad4 AMR exome

AF:

0.692

Gnomad4 ASJ exome

AF:

0.709

Gnomad4 EAS exome

AF:

0.462

Gnomad4 SAS exome

AF:

0.584

Gnomad4 FIN exome

AF:

0.517

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.594

GnomAD4 genome

AF:

0.544

AC:

82643

AN:

151910

Hom.:

23291

Cov.:

AF XY:

0.543

AC XY:

40346

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.403

Gnomad4 AMR

AF:

0.650

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.453

Gnomad4 SAS

AF:

0.573

Gnomad4 FIN

AF:

0.520

Gnomad4 NFE

AF:

0.605

Gnomad4 OTH

AF:

0.609

Alfa

AF:

0.604

Hom.:

59789

Bravo

AF:

0.546

TwinsUK

AF:

0.595

AC:

2208

ALSPAC

AF:

0.602

AC:

2319

ESP6500AA

AF:

0.408

AC:

1278

ESP6500EA

AF:

0.616

AC:

4415

ExAC

AF:

0.583

AC:

70164

Asia WGS

AF:

0.492

AC:

1708

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.7

DANN

Benign

0.46

DEOGEN2

Benign

0.0028

T;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.44

T;T;T

MetaRNN

Benign

0.0000057

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

L;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.040

N;.;N

REVEL

Benign

0.061

Sift

Benign

0.39

T;.;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0050

B;.;.

Vest4

0.11

MPC

0.099

ClinPred

0.0081

GERP RS

5.2

Varity_R

0.082

gMVP

0.040

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