chr2-200609396-C-T

Position:

• chr2-200609396-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001159.4(AOX1):​c.1135C>T​(p.Leu379Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.758

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AOX1	NM_001159.4	c.1135C>T	p.Leu379Phe	missense_variant	12/35	ENST00000374700.7	NP_001150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AOX1	ENST00000374700.7	c.1135C>T	p.Leu379Phe	missense_variant	12/35	1	NM_001159.4	ENSP00000363832.2
AOX1	ENST00000485106.5	n.154C>T		non_coding_transcript_exon_variant	1/22	1
AOX1	ENST00000465297.5	n.177C>T		non_coding_transcript_exon_variant	1/23	2
AOX1	ENST00000485965.5	n.188C>T		non_coding_transcript_exon_variant	1/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.1135C>T (p.L379F) alteration is located in exon 12 (coding exon 12) of the AOX1 gene. This alteration results from a C to T substitution at nucleotide position 1135, causing the leucine (L) at amino acid position 379 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.095
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.011	D
Sift4G	Benign	0.079	T
Polyphen		0.94	P
Vest4		0.52
MutPred		0.75		Gain of ubiquitination at K384 (P = 0.1375);
MVP		0.35
MPC		0.52
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.71
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: chr2-201474119;