dbSNP rs577000059: AOPEP:p.Arg493Arg (chr9-94924098-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001193329.3(AOPEP):c.1477C>A(p.Arg493Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000735 in 1,359,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

AOPEP
NM_001193329.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.79

Publications

0 publications found

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:

ENSG00000224764 (HGNC:58217):

ENSG00000224764 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOPEP	NM_001193329.3 link	c.1477C>A	p.Arg493Arg	synonymous_variant	Exon 6 of 17	ENST00000375315.8	NP_001180258.1	Q8N6M6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOPEP	ENST00000375315.8 link	c.1477C>A	p.Arg493Arg	synonymous_variant	Exon 6 of 17	1	NM_001193329.3	ENSP00000364464.2		Q8N6M6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.35e-7

AC:

AN:

1359950

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670060

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29882

American (AMR)

AF:

0.00

AC:

AN:

31088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24396

East Asian (EAS)

AF:

0.00

AC:

AN:

32618

South Asian (SAS)

AF:

0.00

AC:

AN:

73678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

9.45e-7

AC:

AN:

1058726

Other (OTH)

AF:

0.00

AC:

AN:

56322

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

9.6

(source)

DANN

Benign

0.79

PhyloP100

4.8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over