9-94759925-G-C

Variant names:

• chr9-94759925-G-C
• rs761327668
• NM_001193329.3:c.142G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001193329.3(AOPEP):​c.142G>C​(p.Glu48Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E48K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AOPEP NM_001193329.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.08
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36467806).

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.142G>C	p.Glu48Gln	missense	Exon 2 of 17	NP_001180258.1	Q8N6M6-1
	AOPEP	NM_001386066.1		c.142G>C	p.Glu48Gln	missense	Exon 2 of 16	NP_001372995.1
	AOPEP	NM_001386068.1		c.142G>C	p.Glu48Gln	missense	Exon 3 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.142G>C	p.Glu48Gln	missense	Exon 2 of 17	ENSP00000364464.2	Q8N6M6-1
	AOPEP	ENST00000297979.9	TSL:1	c.142G>C	p.Glu48Gln	missense	Exon 2 of 15	ENSP00000297979.5	Q8N6M6-2
	AOPEP	ENST00000951986.1		c.142G>C	p.Glu48Gln	missense	Exon 2 of 17	ENSP00000622045.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.2	T
PhyloP100		9.1
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.21
Sift	Benign	0.038	D
Sift4G	Uncertain	0.027	D
Vest4		0.43
MVP		0.54
MPC		0.71
ClinPred		0.95	D
GERP RS		4.7
PromoterAI		-0.015	Neutral
gMVP		0.56
Mutation Taster		=87/13	polymorphism

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: rs761327668; hg19: chr9-97522207;