Variant 7-150857308-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001091.4(AOC1):c.838C>T(p.Pro280Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,596,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

AOC1
NM_001091.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

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:

LOC105375567 (HGNC:):

LOC105375567 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022565871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOC1	NM_001091.4 linkuse as main transcript	c.838C>T	p.Pro280Ser	missense_variant	2/5	ENST00000360937.9
LOC105375567	XR_928171.3 linkuse as main transcript	n.123-15863G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOC1	ENST00000360937.9 linkuse as main transcript	c.838C>T	p.Pro280Ser	missense_variant	2/5	1	NM_001091.4	P2	P19801-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000110

AC:

AN:

227602

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

123926

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.0000270

AC:

AN:

1444642

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

716462

show subpopulations

Gnomad4 AFR exome

AF:

0.000936

Gnomad4 AMR exome

AF:

0.0000694

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.0000673

GnomAD4 genome

AF:

0.000289

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.000965

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.000370

ESP6500AA

AF:

0.000250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000746

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.838C>T (p.P280S) alteration is located in exon 2 (coding exon 1) of the AOC1 gene. This alteration results from a C to T substitution at nucleotide position 838, causing the proline (P) at amino acid position 280 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

T;T;T;.;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.22

M_CAP

Benign

0.0020

MetaRNN

Benign

0.023

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.8

M;M;M;M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.5

N;N;N;N;N

REVEL

Benign

0.078

Sift

Benign

0.30

T;T;T;T;T

Sift4G

Benign

0.13

T;T;T;T;T

Polyphen

0.014

B;B;B;.;.

Vest4

0.25

MVP

0.23

MPC

0.21

ClinPred

0.027

GERP RS

3.3

Varity_R

0.062

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over