rs1225253123

Variant names:

• chr2-200595281-C-A
• rs1225253123
• NM_001159.4:c.113C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-200595281-C-A
• chr2-200595281-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001159.4(AOX1):​c.113C>A​(p.Thr38Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,364 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T38I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AOX1 NM_001159.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOX1	NM_001159.4	MANE Select	c.113C>A	p.Thr38Lys	missense	Exon 3 of 35	NP_001150.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AOX1	ENST00000374700.7	TSL:1 MANE Select	c.113C>A	p.Thr38Lys	missense	Exon 3 of 35	ENSP00000363832.2	Q06278
	AOX1	ENST00000854909.1		c.113C>A	p.Thr38Lys	missense	Exon 3 of 36	ENSP00000524968.1
	AOX1	ENST00000854911.1		c.113C>A	p.Thr38Lys	missense	Exon 3 of 35	ENSP00000524970.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250842 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460364 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726512

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.0000224 AC: 1 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111032

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Uncertain	0.58	D
Eigen	Benign	0.087
Eigen_PC	Benign	0.045
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.4
PrimateAI	Uncertain	0.48	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.25
Sift	Benign	0.037	D
Sift4G	Uncertain	0.038	D
Polyphen		0.87	P
Vest4		0.65
MutPred		0.64		Gain of MoRF binding (P = 0.0401)
MVP		0.48
MPC		0.52
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.65
gMVP		0.89
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs1225253123; hg19: chr2-201460004;