17-42845084-T-C

Variant names:

• chr17-42845084-T-C
• rs2144270459
• NM_009590.4:c.458T>C

Variant summary

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

The NM_009590.4(AOC2):​c.458T>C​(p.Val153Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 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. V153G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AOC2 NM_009590.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOC2	NM_009590.4	c.458T>C	p.Val153Ala	missense_variant	Exon 1 of 4	ENST00000253799.8	NP_033720.2
AOC2	NM_001158.5	c.458T>C	p.Val153Ala	missense_variant	Exon 1 of 4		NP_001149.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOC2	ENST00000253799.8	c.458T>C	p.Val153Ala	missense_variant	Exon 1 of 4	1	NM_009590.4	ENSP00000253799.2
AOC2	ENST00000452774.2	c.458T>C	p.Val153Ala	missense_variant	Exon 1 of 4	1		ENSP00000406134.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T;.
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M;M
PhyloP100		1.3
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.064
Sift	Benign	0.054	T;D
Sift4G	Benign	0.10	T;T
Polyphen		0.97	D;D
Vest4		0.52
MutPred		0.29		Loss of catalytic residue at V153 (P = 0.0709);Loss of catalytic residue at V153 (P = 0.0709);
MVP		0.44
MPC		0.031
ClinPred		0.55	D
GERP RS		3.4
PromoterAI		-0.0016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.10
gMVP		0.55

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: rs2144270459; hg19: chr17-40997101;