NM_001193329.3:c.1513G>A

Variant names:

• chr9-94924134-G-A
• rs960335746
• NM_001193329.3:c.1513G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001193329.3(AOPEP):​c.1513G>A​(p.Ala505Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,336,120 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (1 hom.)
• Consequence: AOPEP NM_001193329.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.50
• Publications: 0 publications found

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-AS1 (HGNC:58217):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.844

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193329.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOPEP	NM_001193329.3	MANE Select	c.1513G>A	p.Ala505Thr	missense	Exon 6 of 17	NP_001180258.1	Q8N6M6-1
	AOPEP	NM_001386066.1		c.1513G>A	p.Ala505Thr	missense	Exon 6 of 16	NP_001372995.1
	AOPEP	NM_001386068.1		c.1513G>A	p.Ala505Thr	missense	Exon 7 of 17	NP_001372997.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOPEP	ENST00000375315.8	TSL:1 MANE Select	c.1513G>A	p.Ala505Thr	missense	Exon 6 of 17	ENSP00000364464.2	Q8N6M6-1
	AOPEP	ENST00000297979.9	TSL:1	c.1365-31043G>A		intron	N/A	ENSP00000297979.5	Q8N6M6-2
	AOPEP	ENST00000951986.1		c.1513G>A	p.Ala505Thr	missense	Exon 6 of 17	ENSP00000622045.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000381 AC: 4 AN: 104952 AF XY: 0.0000177

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000135 AC: 18 AN: 1336120 Hom.: 1 Cov.: 30 AF XY: 0.0000168 AC XY: 11 AN XY: 655918

African (AFR) AF: 0.00 AC: 0 AN: 29184

American (AMR) AF: 0.00 AC: 0 AN: 27804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23112

East Asian (EAS) AF: 0.0000931 AC: 3 AN: 32216

South Asian (SAS) AF: 0.000187 AC: 13 AN: 69670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5480

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1046370

Other (OTH) AF: 0.00 AC: 0 AN: 55250

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-1.0	T
PhyloP100		9.5
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.42
Sift	Benign	0.27	T
Sift4G	Uncertain	0.019	D
Vest4		0.88
MutPred		0.82		Gain of glycosylation at A505 (P = 0.0723)
MVP		0.47
MPC		0.83
ClinPred		0.57	D
GERP RS		4.7
gMVP		0.58
Mutation Taster		=16/84	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs960335746; hg19: chr9-97686416;