dbSNP rs1049742: AOC1:p.Ser332Phe (chr7-150857465-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001091.4(AOC1):c.995C>T(p.Ser332Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 1,612,628 control chromosomes in the GnomAD database, including 4,776 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.073 ( 433 hom., cov: 33)

Exomes 𝑓: 0.071 ( 4343 hom. )

Consequence

AOC1
NM_001091.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

53 publications found

Variant links:

Genes affected

AOC1 (HGNC:80): (amine oxidase copper containing 1) This gene encodes a metal-binding membrane glycoprotein that oxidatively deaminates putrescine, histamine, and related compounds. The encoded protein is inhibited by amiloride, a diuretic that acts by closing epithelial sodium ion channels. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

AOC1 links:

ENSG00000289052 (HGNC:):

ENSG00000289052 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039739013).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOC1	NM_001091.4 link	c.995C>T	p.Ser332Phe	missense_variant	Exon 2 of 5	ENST00000360937.9	NP_001082.2	P19801-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOC1	ENST00000360937.9 link	c.995C>T	p.Ser332Phe	missense_variant	Exon 2 of 5	1	NM_001091.4	ENSP00000354193.4		P19801-1

Frequencies

GnomAD3 genomes

AF:

0.0727

AC:

11063

AN:

152194

Hom.:

433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0930

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.0462

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0279

Gnomad FIN

AF:

0.0650

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0766

Gnomad OTH

AF:

0.0670

GnomAD2 exomes

AF:

0.0575

AC:

14200

AN:

247160

AF XY:

0.0567

show subpopulations

Gnomad AFR exome

AF:

0.0920

Gnomad AMR exome

AF:

0.0301

Gnomad ASJ exome

AF:

0.0482

Gnomad EAS exome

AF:

0.00179

Gnomad FIN exome

AF:

0.0711

Gnomad NFE exome

AF:

0.0757

Gnomad OTH exome

AF:

0.0526

GnomAD4 exome

AF:

0.0706

AC:

103135

AN:

1460316

Hom.:

4343

Cov.:

AF XY:

0.0688

AC XY:

49983

AN XY:

726454

show subpopulations

African (AFR)

AF:

0.0920

AC:

3079

AN:

33472

American (AMR)

AF:

0.0324

AC:

1448

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0511

AC:

1334

AN:

26124

East Asian (EAS)

AF:

0.000806

AC:

AN:

39690

South Asian (SAS)

AF:

0.0299

AC:

2581

AN:

86240

European-Finnish (FIN)

AF:

0.0729

AC:

3809

AN:

52220

Middle Eastern (MID)

AF:

0.0329

AC:

190

AN:

5768

European-Non Finnish (NFE)

AF:

0.0782

AC:

86911

AN:

1111724

Other (OTH)

AF:

0.0621

AC:

3751

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

6552

13104

19656

26208

32760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3192

6384

9576

12768

15960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0726

AC:

11062

AN:

152312

Hom.:

433

Cov.:

AF XY:

0.0697

AC XY:

5188

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0927

AC:

3853

AN:

41574

American (AMR)

AF:

0.0461

AC:

706

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0519

AC:

180

AN:

3468

East Asian (EAS)

AF:

0.00251

AC:

AN:

5182

South Asian (SAS)

AF:

0.0282

AC:

136

AN:

4830

European-Finnish (FIN)

AF:

0.0650

AC:

691

AN:

10624

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0766

AC:

5208

AN:

68010

Other (OTH)

AF:

0.0663

AC:

140

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

540

1080

1621

2161

2701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0712

Hom.:

1481

Bravo

AF:

0.0724

TwinsUK

AF:

0.0823

AC:

305

ALSPAC

AF:

0.0732

AC:

282

ESP6500AA

AF:

0.0861

AC:

379

ESP6500EA

AF:

0.0738

AC:

634

ExAC

AF:

0.0591

AC:

7172

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0705

EpiControl

AF:

0.0706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;T;.;T

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.89

.;D;.;D;T

MetaRNN

Benign

0.0040

T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.0

M;M;M;M;.

PhyloP100

1.4

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0050

D;D;D;T;D

Sift4G

Uncertain

0.030

D;D;D;D;D

Polyphen

0.99

D;D;D;.;.

Vest4

0.089

MPC

0.83

ClinPred

0.037

GERP RS

5.0

Varity_R

0.51

gMVP

0.70

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over