NM_009590.4:c.205C>G

Variant names:

• chr17-42844831-C-G
• rs150378203
• NM_009590.4:c.205C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_009590.4(AOC2):​c.205C>G​(p.Arg69Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. R69H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AOC2 NM_009590.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 0 publications found

Genes affected

AOC2 (HGNC:549): (amine oxidase copper containing 2) Copper amine oxidases catalyze the oxidative conversion of amines to aldehydes and ammonia in the presence of copper and quinone cofactor. This gene shows high sequence similarity to copper amine oxidases from various species ranging from bacteria to mammals. The protein contains several conserved motifs including the active site of amine oxidases and the histidine residues that likely bind copper. It may be a critical modulator of signal transmission in retina, possibly by degrading the biogenic amines dopamine, histamine, and putrescine. This gene may be a candidate gene for hereditary ocular diseases. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

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 (MetaRNN=0.06924242).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_009590.4. 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
	AOC2	NM_009590.4	MANE Select	c.205C>G	p.Arg69Gly	missense	Exon 1 of 4	NP_033720.2	O75106-1
	AOC2	NM_001158.5		c.205C>G	p.Arg69Gly	missense	Exon 1 of 4	NP_001149.2	O75106-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOC2	ENST00000253799.8	TSL:1 MANE Select	c.205C>G	p.Arg69Gly	missense	Exon 1 of 4	ENSP00000253799.2	O75106-1
	AOC2	ENST00000452774.2	TSL:1	c.205C>G	p.Arg69Gly	missense	Exon 1 of 4	ENSP00000406134.1	O75106-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250912 AF XY: 0.00

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460638 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726376

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111086

Other (OTH) AF: 0.00 AC: 0 AN: 60300

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	0.051
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.54	N
PhyloP100		0.39
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.039
Sift	Benign	0.12	T
Sift4G	Benign	0.19	T
Polyphen		0.0030	B
Vest4		0.16
MutPred		0.57		Loss of stability (P = 0.0524)
MVP		0.26
MPC		0.031
ClinPred		0.039	T
GERP RS		-3.2
PromoterAI		-0.056	Neutral
Varity_R		0.11
gMVP		0.26

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: rs150378203; hg19: chr17-40996848;