7-150856538-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001091.4(AOC1):​c.68C>T​(p.Pro23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,613,974 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

AOC1
NM_001091.4 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.27
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.046766073).
BP6
Variant 7-150856538-C-T is Benign according to our data. Variant chr7-150856538-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2518901.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AOC1NM_001091.4 linkc.68C>T p.Pro23Leu 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
AOC1ENST00000360937.9 linkc.68C>T p.Pro23Leu missense_variant Exon 2 of 5 1 NM_001091.4 ENSP00000354193.4 P19801-1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152146
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000108
AC:
27
AN:
249384
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135348
show subpopulations
Gnomad AFR exome
AF:
0.0000647
Gnomad AMR exome
AF:
0.0000580
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000203
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000301
AC:
440
AN:
1461828
Hom.:
2
Cov.:
33
AF XY:
0.000305
AC XY:
222
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000365
Gnomad4 OTH exome
AF:
0.000397
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152146
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000187
Hom.:
0
Bravo
AF:
0.000113
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000121
AC:
1
ExAC
AF:
0.0000910
AC:
11
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 20, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.14
DANN
Benign
0.50
DEOGEN2
Benign
0.18
T;T;.;T;.;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0080
N
LIST_S2
Benign
0.40
.;T;T;.;T;T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.047
T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.8
M;M;.;M;M;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.9
N;N;N;N;N;N
REVEL
Benign
0.012
Sift
Benign
0.34
T;T;T;T;T;T
Sift4G
Benign
0.16
T;T;T;T;T;T
Polyphen
0.40
B;B;.;B;.;.
Vest4
0.082
MVP
0.067
MPC
0.21
ClinPred
0.041
T
GERP RS
-2.2
Varity_R
0.028
gMVP
0.27

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.

Other links and lift over

dbSNP: rs201476675; hg19: chr7-150553626; COSMIC: COSV100710943; COSMIC: COSV100710943; API