9-94924098-C-A

Variant names:

• chr9-94924098-C-A
• rs577000059
• NM_001193329.3:c.1477C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).

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.1477C>A	p.Arg493Arg	synonymous	Exon 6 of 17	NP_001180258.1	Q8N6M6-1
	AOPEP	NM_001386066.1		c.1477C>A	p.Arg493Arg	synonymous	Exon 6 of 16	NP_001372995.1
	AOPEP	NM_001386068.1		c.1477C>A	p.Arg493Arg	synonymous	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.1477C>A	p.Arg493Arg	synonymous	Exon 6 of 17	ENSP00000364464.2	Q8N6M6-1
	AOPEP	ENST00000297979.9	TSL:1	c.1365-31079C>A		intron	N/A	ENSP00000297979.5	Q8N6M6-2
	AOPEP	ENST00000951986.1		c.1477C>A	p.Arg493Arg	synonymous	Exon 6 of 17	ENSP00000622045.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.35e-7 AC: 1 AN: 1359950 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 670060

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

African (AFR) AF: 0.00 AC: 0 AN: 29882

American (AMR) AF: 0.00 AC: 0 AN: 31088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24396

East Asian (EAS) AF: 0.00 AC: 0 AN: 32618

South Asian (SAS) AF: 0.00 AC: 0 AN: 73678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 9.45e-7 AC: 1 AN: 1058726

Other (OTH) AF: 0.00 AC: 0 AN: 56322

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	9.6
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

Other links and lift over

dbSNP: rs577000059; hg19: chr9-97686380;