dbSNP rs773593619: AOC1:p.Ser245Asn (chr7-150857204-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001091.4(AOC1):c.734G>A(p.Ser245Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. S245I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AOC1
NM_001091.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.17

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18729976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOC1	NM_001091.4 link	c.734G>A	p.Ser245Asn	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.734G>A	p.Ser245Asn	missense_variant	Exon 2 of 5	1	NM_001091.4	ENSP00000354193.4		P19801-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248044

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134526

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460706

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726544

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.20

T;T;.;T;.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.63

.;T;T;.;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.19

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.;M;M;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.8

N;N;N;N;N;N

REVEL

Benign

0.049

Sift

Uncertain

0.029

D;D;D;D;D;T

Sift4G

Benign

0.13

T;T;D;T;T;D

Polyphen

0.0010

B;B;.;B;.;.

Vest4

0.15

MutPred

0.39

Gain of ubiquitination at K241 (P = 0.0913);Gain of ubiquitination at K241 (P = 0.0913);Gain of ubiquitination at K241 (P = 0.0913);Gain of ubiquitination at K241 (P = 0.0913);Gain of ubiquitination at K241 (P = 0.0913);Gain of ubiquitination at K241 (P = 0.0913);

MVP

0.19

MPC

0.20

ClinPred

0.16

GERP RS

2.9

Varity_R

0.15

gMVP

0.76

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over