rs3731722

Variant names:

• chr2-200669666-A-C
• NM_001159.4:c.3890A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-200669666-A-C
• chr2-200669666-A-G
• chr2-200669666-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001159.4(AOX1):​c.3890A>C​(p.His1297Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. H1297R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AOX1 NM_001159.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025904924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOX1	NM_001159.4	c.3890A>C	p.His1297Pro	missense_variant	Exon 34 of 35	ENST00000374700.7	NP_001150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOX1	ENST00000374700.7	c.3890A>C	p.His1297Pro	missense_variant	Exon 34 of 35	1	NM_001159.4	ENSP00000363832.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.0030
DANN	Benign	0.19
DEOGEN2	Benign	0.093	T;T;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.17	T;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.026	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.0	N;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.51	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.14
MutPred		0.34		Gain of glycosylation at H1297 (P = 0.0396);.;.;
MVP		0.095
MPC		0.15
ClinPred		0.24	T
GERP RS		-11
Varity_R		0.29
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-201534389;