NM_001193329.3:c.308G>A

Variant names:

• chr9-94760091-G-A
• rs118018100
• NM_001193329.3:c.308G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001193329.3(AOPEP):​c.308G>A​(p.Ser103Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,614,146 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (41 hom.)
• Consequence: AOPEP NM_001193329.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.651
• Publications: 5 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032122731).
• BP6: Variant 9-94760091-G-A is Benign according to our data. Variant chr9-94760091-G-A is described in ClinVar as Benign. ClinVar VariationId is 769754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00158 (241/152262) while in subpopulation EAS AF = 0.017 (88/5188). AF 95% confidence interval is 0.0141. There are 3 homozygotes in GnomAd4. There are 137 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.308G>A	p.Ser103Asn	missense	Exon 2 of 17	NP_001180258.1	Q8N6M6-1
	AOPEP	NM_001386066.1		c.308G>A	p.Ser103Asn	missense	Exon 2 of 16	NP_001372995.1
	AOPEP	NM_001386068.1		c.308G>A	p.Ser103Asn	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.308G>A	p.Ser103Asn	missense	Exon 2 of 17	ENSP00000364464.2	Q8N6M6-1
	AOPEP	ENST00000297979.9	TSL:1	c.308G>A	p.Ser103Asn	missense	Exon 2 of 15	ENSP00000297979.5	Q8N6M6-2
	AOPEP	ENST00000951986.1		c.308G>A	p.Ser103Asn	missense	Exon 2 of 17	ENSP00000622045.1

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 238 AN: 152144 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00878

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00400 AC: 1004 AN: 251234 AF XY: 0.00326

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0220

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0117

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000969

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00166 AC: 2425 AN: 1461884 Hom.: 41 Cov.: 31 AF XY: 0.00152 AC XY: 1105 AN XY: 727248

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0198 AC: 887 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0352 AC: 1398 AN: 39700

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1112002

Other (OTH) AF: 0.000844 AC: 51 AN: 60396

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152262 Hom.: 3 Cov.: 32 AF XY: 0.00184 AC XY: 137 AN XY: 74434

African (AFR) AF: 0.000168 AC: 7 AN: 41566

American (AMR) AF: 0.00896 AC: 137 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.0170 AC: 88 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000967 Hom.: 5

Bravo AF: 0.00249

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00347 AC: 421

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	17
DANN	Benign	0.97
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.65
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.043
Sift	Benign	0.15	T
Sift4G	Benign	0.20	T
Vest4		0.070
MVP		0.33
MPC		0.22
ClinPred		0.0064	T
GERP RS		2.1
PromoterAI		0.0027	Neutral
gMVP		0.17
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs118018100; hg19: chr9-97522373;