rs33986943

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-42852620-G-A
• chr17-42852620-G-C
• chr17-42852620-G-T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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: 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
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
AOC3	NM_003734.4	c.1277G>A	p.Arg426His	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>A	p.Arg426His	missense_variant	Exon 1 of 4	1	NM_003734.4	ENSP00000312326.1
AOC3	ENST00000613571.1	c.1277G>A	p.Arg426His	missense_variant	Exon 1 of 3	1		ENSP00000484312.1
AOC3	ENST00000587330.1	n.-134G>A		upstream_gene_variant		5		ENSP00000464787.1

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

GnomAD2 exomes AF: 0.0741 AC: 18634 AN: 251438 AF XY: 0.0776

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 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

African (AFR) AF: 0.0146 AC: 488 AN: 33480

American (AMR) AF: 0.0499 AC: 2232 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 1772 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39682

South Asian (SAS) AF: 0.0837 AC: 7217 AN: 86258

European-Finnish (FIN) AF: 0.0710 AC: 3794 AN: 53420

Middle Eastern (MID) AF: 0.0973 AC: 561 AN: 5768

European-Non Finnish (NFE) AF: 0.105 AC: 117093 AN: 1112006

Other (OTH) AF: 0.0817 AC: 4935 AN: 60396

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

African (AFR) AF: 0.0201 AC: 835 AN: 41542

American (AMR) AF: 0.0641 AC: 981 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0711 AC: 247 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0808 AC: 390 AN: 4824

European-Finnish (FIN) AF: 0.0662 AC: 701 AN: 10594

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6829 AN: 68008

Other (OTH) AF: 0.0777 AC: 164 AN: 2112

Alfa AF: 0.0855 Hom.: 1408

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
PhyloP100		-0.37
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
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs33986943; hg19: chr17-41004637; COSMIC: COSV107275128; COSMIC: COSV107275128;