rs55754655

Positions:

• chr2-200661607-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

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]

ACMG classification

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	UniProt
AOX1	NM_001159.4	c.3404A>G	p.Asn1135Ser	missense_variant	30/35	ENST00000374700.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23381 AN: 152094 Hom.: 2165 Cov.: 33

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

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.: 30 AF XY: 0.125 AC XY: 90339 AN XY: 723920

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.: 33 AF XY: 0.148 AC XY: 10981 AN XY: 74426

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	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.18
DEOGEN2	Benign	0.067	T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.63	T;T
MetaRNN	Benign	0.0048	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.38	T
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	T
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

Other links and lift over

dbSNP: rs55754655; hg19: chr2-201526330;