17-42845048-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_009590.4(AOC2):c.422C>T(p.Pro141Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000931 in 1,613,940 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0047 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 13 hom. )

Consequence

AOC2
NM_009590.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.68

Variant links:

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]

AOC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016773641).

BP6

Variant 17-42845048-C-T is Benign according to our data. Variant chr17-42845048-C-T is described in ClinVar as [Benign]. Clinvar id is 714859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOC2	NM_009590.4 link	c.422C>T	p.Pro141Leu	missense_variant	Exon 1 of 4	ENST00000253799.8	NP_033720.2	O75106-1
AOC2	NM_001158.5 link	c.422C>T	p.Pro141Leu	missense_variant	Exon 1 of 4		NP_001149.2	O75106-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOC2	ENST00000253799.8 link	c.422C>T	p.Pro141Leu	missense_variant	Exon 1 of 4	1	NM_009590.4	ENSP00000253799.2		O75106-1
AOC2	ENST00000452774.2 link	c.422C>T	p.Pro141Leu	missense_variant	Exon 1 of 4	1		ENSP00000406134.1		O75106-2

Frequencies

GnomAD3 genomes

AF:

0.00475

AC:

723

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00132

AC:

330

AN:

249934

AF XY:

0.00101

show subpopulations

Gnomad AFR exome

AF:

0.0157

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.000534

AC:

780

AN:

1461594

Hom.:

Cov.:

AF XY:

0.000480

AC XY:

349

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.0154

AC:

516

AN:

33480

American (AMR)

AF:

0.00161

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53148

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000818

AC:

AN:

1112004

Other (OTH)

AF:

0.00136

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

149

198

248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00475

AC:

723

AN:

152346

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

332

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0159

AC:

659

AN:

41574

American (AMR)

AF:

0.00300

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68028

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.00522

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00152

AC:

185

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.017

T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Pathogenic

3.5

M;M

PhyloP100

7.7

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-9.2

D;D

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.75

MVP

0.91

MPC

0.21

ClinPred

0.10

GERP RS

2.9

PromoterAI

0.0014

Neutral

(source)

Varity_R

0.92

gMVP

0.91

Mutation Taster

=91/9

polymorphism

(source)

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

Publications

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17-42845048-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over