rs55754655

Variant names:

• chr2-200661607-A-C
• rs55754655
• NM_001159.4:c.3404A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-200661607-A-C
• chr2-200661607-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001159.4(AOX1):​c.3404A>C​(p.Asn1135Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AOX1 NM_001159.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38353425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOX1	NM_001159.4	c.3404A>C	p.Asn1135Thr	missense_variant	Exon 30 of 35	ENST00000374700.7	NP_001150.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOX1	ENST00000374700.7	c.3404A>C	p.Asn1135Thr	missense_variant	Exon 30 of 35	1	NM_001159.4	ENSP00000363832.2
AOX1	ENST00000485106.5	n.2143A>C		non_coding_transcript_exon_variant	Exon 17 of 22	1
AOX1	ENST00000260930.10	c.62A>C	p.Asn21Thr	missense_variant	Exon 2 of 7	5		ENSP00000260930.6
AOX1	ENST00000465297.5	n.2336A>C		non_coding_transcript_exon_variant	Exon 18 of 23	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459638 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726238

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33338

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110198

Other (OTH) AF: 0.00 AC: 0 AN: 60314

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.095	T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L;.
PhyloP100		2.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.31	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.039	D;D
Polyphen		0.0010	B;.
Vest4		0.28
MutPred		0.52		Loss of sheet (P = 0.1158);.;
MVP		0.34
MPC		0.11
ClinPred		0.69	D
GERP RS		5.3
Varity_R		0.44
gMVP		0.38
Mutation Taster		=71/29	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: rs55754655; hg19: chr2-201526330;