Variant chr9-94924026-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_001193329.3(AOPEP):c.1405G>A(p.Gly469Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,499,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 0 hom. )

Consequence

AOPEP
NM_001193329.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.188

Variant links:

Genes affected

AOPEP (HGNC:1361): (aminopeptidase O (putative)) This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

AOPEP links:

AOPEP (HGNC:):

AOPEP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012637883).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000486 (74/152336) while in subpopulation AMR AF= 0.00118 (18/15302). AF 95% confidence interval is 0.00076. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOPEP	NM_001193329.3 linkuse as main transcript	c.1405G>A	p.Gly469Arg	missense_variant	6/17	ENST00000375315.8	NP_001180258.1	Q8N6M6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOPEP	ENST00000375315.8 linkuse as main transcript	c.1405G>A	p.Gly469Arg	missense_variant	6/17	1	NM_001193329.3	ENSP00000364464.2		Q8N6M6-1

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000518

AC:

AN:

112008

Hom.:

AF XY:

0.000478

AC XY:

AN XY:

60624

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000939

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000126

Gnomad NFE exome

AF:

0.000836

Gnomad OTH exome

AF:

0.00158

GnomAD4 exome

AF:

0.000812

AC:

1094

AN:

1347072

Hom.:

Cov.:

AF XY:

0.000760

AC XY:

504

AN XY:

662804

show subpopulations

Gnomad4 AFR exome

AF:

0.000102

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000211

Gnomad4 NFE exome

AF:

0.000969

Gnomad4 OTH exome

AF:

0.000645

GnomAD4 genome

AF:

0.000486

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000612

Hom.:

Bravo

AF:

0.000563

ExAC

AF:

0.000151

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

AOPEP: PM2:Supporting, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.28

DANN

Benign

0.79

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.38

T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Benign

0.097

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.28

T;T;T

Vest4

0.16

MutPred

0.65

Gain of methylation at G469 (P = 0.0402);Gain of methylation at G469 (P = 0.0402);.;

MVP

0.22

MPC

0.27

ClinPred

0.024

GERP RS

-7.2

gMVP

0.30

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over