2-200613862-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001159.4(AOX1):c.1507C>G(p.Leu503Val) variant causes a missense change. The variant allele was found at a frequency of 0.00026 in 1,612,700 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. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 0 hom. )
Consequence
AOX1
NM_001159.4 missense
NM_001159.4 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 3.66
Genes affected
AOX1 (HGNC:553): (aldehyde oxidase 1) Aldehyde oxidase produces hydrogen peroxide and, under certain conditions, can catalyze the formation of superoxide. Aldehyde oxidase is a candidate gene for amyotrophic lateral sclerosis. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
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=0.16248074).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AOX1 | NM_001159.4 | c.1507C>G | p.Leu503Val | missense_variant | 15/35 | ENST00000374700.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AOX1 | ENST00000374700.7 | c.1507C>G | p.Leu503Val | missense_variant | 15/35 | 1 | NM_001159.4 | P1 | |
AOX1 | ENST00000485106.5 | n.416C>G | non_coding_transcript_exon_variant | 3/22 | 1 | ||||
AOX1 | ENST00000465297.5 | n.439C>G | non_coding_transcript_exon_variant | 3/23 | 2 | ||||
AOX1 | ENST00000485965.5 | n.560C>G | non_coding_transcript_exon_variant | 4/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152156Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
22
AN:
152156
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000159 AC: 40AN: 250844Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135554
GnomAD3 exomes
AF:
AC:
40
AN:
250844
Hom.:
AF XY:
AC XY:
22
AN XY:
135554
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000273 AC: 398AN: 1460426Hom.: 0 Cov.: 30 AF XY: 0.000257 AC XY: 187AN XY: 726550
GnomAD4 exome
AF:
AC:
398
AN:
1460426
Hom.:
Cov.:
30
AF XY:
AC XY:
187
AN XY:
726550
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74450
GnomAD4 genome
?
AF:
AC:
22
AN:
152274
Hom.:
Cov.:
32
AF XY:
AC XY:
10
AN XY:
74450
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
13
EpiCase
AF:
EpiControl
AF:
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 | Oct 18, 2021 | The c.1507C>G (p.L503V) alteration is located in exon 15 (coding exon 15) of the AOX1 gene. This alteration results from a C to G substitution at nucleotide position 1507, causing the leucine (L) at amino acid position 503 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at