rs45558339

Variant names:

• chr7-150857907-G-A
• rs45558339
• NM_001091.4:c.1437G>A
• AOC1 p.Met479Ile

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001091.4(AOC1):​c.1437G>A​(p.Met479Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,613,378 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00014 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: AOC1 NM_001091.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436
• Publications: 5 publications found

Genes affected

AOC1 (HGNC:80): (amine oxidase copper containing 1) This gene encodes a metal-binding membrane glycoprotein that oxidatively deaminates putrescine, histamine, and related compounds. The encoded protein is inhibited by amiloride, a diuretic that acts by closing epithelial sodium ion channels. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

ENSG00000289052 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01112026).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001091.4. 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
	AOC1	NM_001091.4	MANE Select	c.1437G>A	p.Met479Ile	missense	Exon 2 of 5	NP_001082.2	P19801-1
	AOC1	NM_001272072.2		c.1437G>A	p.Met479Ile	missense	Exon 2 of 5	NP_001259001.1	P19801-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOC1	ENST00000360937.9	TSL:1 MANE Select	c.1437G>A	p.Met479Ile	missense	Exon 2 of 5	ENSP00000354193.4	P19801-1
	AOC1	ENST00000416793.6	TSL:1	c.1437G>A	p.Met479Ile	missense	Exon 2 of 5	ENSP00000411613.2	P19801-2
	AOC1	ENST00000941409.1		c.1437G>A	p.Met479Ile	missense	Exon 3 of 6	ENSP00000611468.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152200 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000362 AC: 90 AN: 248646 AF XY: 0.000311

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00468

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000131 AC: 192 AN: 1461060 Hom.: 0 Cov.: 33 AF XY: 0.000125 AC XY: 91 AN XY: 726792

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00416 AC: 165 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53034

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111724

Other (OTH) AF: 0.000116 AC: 7 AN: 60376

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152318 Hom.: 1 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74480

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000212 Hom.: 0

Bravo AF: 0.000219

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.085	T
Eigen	Benign	0.013
Eigen_PC	Benign	0.086
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.44
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.095
Sift	Benign	0.048	D
Sift4G	Benign	0.27	T
Varity_R		0.34
gMVP		0.70
Mutation Taster		=97/3	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs45558339;

hg19: chr7-150554995;