rs33986943

chr17-42852620-G-Achr17-42852620-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003734.4(AOC3):c.1277G>A(p.Arg426His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 1,614,108 control chromosomes in the GnomAD database, including 7,652 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.068 (476 hom., cov: 32)
  • Exomes 𝑓: 0.094 (7176 hom.)
• Consequence: AOC3 NM_003734.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017941296).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOC3	NM_003734.4	c.1277G>A	p.Arg426His	missense_variant	1/4	ENST00000308423.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOC3	ENST00000308423.7	c.1277G>A	p.Arg426His	missense_variant	1/4	1	NM_003734.4	P1
AOC3	ENST00000613571.1	c.1277G>A	p.Arg426His	missense_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10303 AN: 152120 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0711

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0808

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0785

GnomAD3 exomes AF: 0.0741 AC: 18634 AN: 251438 Hom.: 868 AF XY: 0.0776 AC XY: 10539 AN XY: 135890

Gnomad AFR exome AF: 0.0178

Gnomad AMR exome AF: 0.0478

Gnomad ASJ exome AF: 0.0692

Gnomad EAS exome AF: 0.000327

Gnomad SAS exome AF: 0.0839

Gnomad FIN exome AF: 0.0681

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.0824

GnomAD4 exome AF: 0.0945 AC: 138102 AN: 1461870 Hom.: 7176 Cov.: 33 AF XY: 0.0943 AC XY: 68568 AN XY: 727228

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.0499

Gnomad4 ASJ exome AF: 0.0678

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0837

Gnomad4 FIN exome AF: 0.0710

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.0817

GnomAD4 genome AF: 0.0677 AC: 10302 AN: 152238 Hom.: 476 Cov.: 32 AF XY: 0.0662 AC XY: 4924 AN XY: 74424

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.0641

Gnomad4 ASJ AF: 0.0711

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0808

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0897 Hom.: 1102

Bravo AF: 0.0647

TwinsUK AF: 0.122 AC: 454

ALSPAC AF: 0.106 AC: 409

ESP6500AA AF: 0.0216 AC: 95

ESP6500EA AF: 0.102 AC: 874

ExAC AF: 0.0745 AC: 9050

Asia WGS AF: 0.0350 AC: 122 AN: 3478

EpiCase AF: 0.0977

EpiControl AF: 0.0991

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.7
Dann	Benign	0.93
DEOGEN2	Benign	0.099	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.81	T;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.1	N;.
REVEL	Benign	0.045
Sift	Benign	0.16	T;.
Sift4G	Benign	0.17	T;T
Polyphen		0.021	B;.
Vest4		0.018
MPC		0.46
ClinPred		0.0012	T
GERP RS		-3.7
Varity_R		0.14
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs33986943; hg19: chr17-41004637;