chr17-42852620-G-C

Variant names:

• chr17-42852620-G-C
• rs33986943
• NM_003734.4:c.1277G>C

Variant summary

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

The NM_003734.4(AOC3):​c.1277G>C​(p.Arg426Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R426C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AOC3 NM_003734.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 21 publications found

Genes affected

AOC3 (HGNC:550): (amine oxidase copper containing 3) This gene encodes a member of the semicarbazide-sensitive amine oxidase family. Copper amine oxidases catalyze the oxidative conversion of amines to aldehydes in the presence of copper and quinone cofactor. The encoded protein is localized to the cell surface, has adhesive properties as well as monoamine oxidase activity, and may be involved in leukocyte trafficking. Alterations in levels of the encoded protein may be associated with many diseases, including diabetes mellitus. A pseudogene of this gene has been described and is located approximately 9-kb downstream on the same chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

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=0.07316023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOC3	NM_003734.4	c.1277G>C	p.Arg426Pro	missense_variant	Exon 1 of 4	ENST00000308423.7	NP_003725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOC3	ENST00000308423.7	c.1277G>C	p.Arg426Pro	missense_variant	Exon 1 of 4	1	NM_003734.4	ENSP00000312326.1
AOC3	ENST00000613571.1	c.1277G>C	p.Arg426Pro	missense_variant	Exon 1 of 3	1		ENSP00000484312.1
AOC3	ENST00000587330.1	n.-134G>C		upstream_gene_variant		5		ENSP00000464787.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.6
DANN	Benign	0.67
DEOGEN2	Benign	0.058	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.060	N;N
PhyloP100		-0.37
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.4	N;.
REVEL	Benign	0.037
Sift	Benign	0.42	T;.
Sift4G	Benign	0.27	T;T
Polyphen		0.010	B;.
Vest4		0.13
MutPred		0.47		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.085
MPC		0.86
ClinPred		0.071	T
GERP RS		-3.7
Varity_R		0.66
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs33986943; hg19: chr17-41004637;