2-200636959-C-T

Variant names:

• chr2-200636959-C-T
• NM_001159.4:c.2395C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001159.4(AOX1):​c.2395C>T​(p.His799Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AOX1 NM_001159.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.61

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOX1	NM_001159.4	c.2395C>T	p.His799Tyr	missense_variant	Exon 22 of 35	ENST00000374700.7	NP_001150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOX1	ENST00000374700.7	c.2395C>T	p.His799Tyr	missense_variant	Exon 22 of 35	1	NM_001159.4	ENSP00000363832.2
AOX1	ENST00000485106.5	n.1134C>T		non_coding_transcript_exon_variant	Exon 9 of 22	1
AOX1	ENST00000465297.5	n.1327C>T		non_coding_transcript_exon_variant	Exon 10 of 23	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.84	P
Vest4		0.41
MutPred		0.53		Gain of methylation at K795 (P = 0.0542);
MVP		0.66
MPC		0.53
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.85
gMVP		0.65

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: chr2-201501682;