Variant rs55754655 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001159.4(AOX1):c.3404A>G(p.Asn1135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,606,880 control chromosomes in the GnomAD database, including 15,610 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2171 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13439 hom. )

Consequence

AOX1
NM_001159.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19

Variant links:

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]

AOX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047774613).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOX1	NM_001159.4 linkuse as main transcript	c.3404A>G	p.Asn1135Ser	missense_variant	30/35	ENST00000374700.7	NP_001150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
AOX1	ENST00000374700.7 linkuse as main transcript	c.3404A>G	p.Asn1135Ser	missense_variant	30/35	1	NM_001159.4	ENSP00000363832	P1
AOX1	ENST00000485106.5 linkuse as main transcript	n.2143A>G		non_coding_transcript_exon_variant	17/22	1
AOX1	ENST00000260930.10 linkuse as main transcript	c.62A>G	p.Asn21Ser	missense_variant	2/7	5		ENSP00000260930
AOX1	ENST00000465297.5 linkuse as main transcript	n.2336A>G		non_coding_transcript_exon_variant	18/23	2

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23381

AN:

152094

Hom.:

2165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0953

Gnomad EAS

AF:

0.00423

Gnomad SAS

AF:

0.0375

Gnomad FIN

AF:

0.0876

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.146

GnomAD3 exomes

AF:

0.109

AC:

27197

AN:

250104

Hom.:

1919

AF XY:

0.105

AC XY:

14157

AN XY:

135190

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.0701

Gnomad ASJ exome

AF:

0.0933

Gnomad EAS exome

AF:

0.00288

Gnomad SAS exome

AF:

0.0429

Gnomad FIN exome

AF:

0.0916

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.128

AC:

186705

AN:

1454668

Hom.:

13439

Cov.:

AF XY:

0.125

AC XY:

90339

AN XY:

723920

show subpopulations

Gnomad4 AFR exome

AF:

0.254

Gnomad4 AMR exome

AF:

0.0747

Gnomad4 ASJ exome

AF:

0.0942

Gnomad4 EAS exome

AF:

0.00182

Gnomad4 SAS exome

AF:

0.0449

Gnomad4 FIN exome

AF:

0.0970

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.154

AC:

23416

AN:

152212

Hom.:

2171

Cov.:

AF XY:

0.148

AC XY:

10981

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.256

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.0953

Gnomad4 EAS

AF:

0.00424

Gnomad4 SAS

AF:

0.0375

Gnomad4 FIN

AF:

0.0876

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.136

Hom.:

2704

Bravo

AF:

0.161

TwinsUK

AF:

0.145

AC:

539

ALSPAC

AF:

0.141

AC:

544

ESP6500AA

AF:

0.258

AC:

1137

ESP6500EA

AF:

0.130

AC:

1116

ExAC

AF:

0.115

AC:

13983

Asia WGS

AF:

0.0440

AC:

154

AN:

3478

EpiCase

AF:

0.133

EpiControl

AF:

0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.037

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.18

DEOGEN2

Benign

0.067

T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

2.4

N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.057

MPC

0.077

ClinPred

0.0041

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.16

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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