Variant 9-94759925-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001193329.3(AOPEP):c.142G>A(p.Glu48Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

AOPEP
NM_001193329.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.08

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOPEP	NM_001193329.3 linkuse as main transcript	c.142G>A	p.Glu48Lys	missense_variant	2/17	ENST00000375315.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOPEP	ENST00000375315.8 linkuse as main transcript	c.142G>A	p.Glu48Lys	missense_variant	2/17	1	NM_001193329.3	P1	Q8N6M6-1
AOPEP	ENST00000297979.9 linkuse as main transcript	c.142G>A	p.Glu48Lys	missense_variant	2/15	1			Q8N6M6-2
AOPEP	ENST00000277198.6 linkuse as main transcript	c.142G>A	p.Glu48Lys	missense_variant	2/8	2			Q8N6M6-3
AOPEP	ENST00000489318.2 linkuse as main transcript	n.425G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251474

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Jul 01, 2022

AOPEP: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.33

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.031

D;T;D

Sift4G

Uncertain

0.022

D;D;D

Vest4

0.54

MutPred

0.54

Gain of methylation at E48 (P = 0.0177);Gain of methylation at E48 (P = 0.0177);Gain of methylation at E48 (P = 0.0177);

MVP

0.52

MPC

0.80

ClinPred

0.89

GERP RS

4.7

gMVP

0.72

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