rs773937413
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001032386.2(SUOX):c.98delA(p.Asn33fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
SUOX
NM_001032386.2 frameshift
NM_001032386.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.628
Genes affected
SUOX (HGNC:11460): (sulfite oxidase) Sulfite oxidase is a homodimeric protein localized to the intermembrane space of mitochondria. Each subunit contains a heme domain and a molybdopterin-binding domain. The enzyme catalyzes the oxidation of sulfite to sulfate, the final reaction in the oxidative degradation of the sulfur amino acids cysteine and methionine. Sulfite oxidase deficiency results in neurological abnormalities which are often fatal at an early age. Alternative splicing results in multiple transcript variants encoding identical proteins. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 21 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-56002587-CA-C is Pathogenic according to our data. Variant chr12-56002587-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 529474.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SUOX | NM_001032386.2 | c.98delA | p.Asn33fs | frameshift_variant | 4/5 | ENST00000266971.8 | NP_001027558.1 | |
SUOX | NM_000456.3 | c.98delA | p.Asn33fs | frameshift_variant | 5/6 | NP_000447.2 | ||
SUOX | NM_001032387.2 | c.98delA | p.Asn33fs | frameshift_variant | 3/4 | NP_001027559.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SUOX | ENST00000266971.8 | c.98delA | p.Asn33fs | frameshift_variant | 4/5 | 2 | NM_001032386.2 | ENSP00000266971.3 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251486Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727248
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GnomAD4 genome Cov.: 31
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Sulfite oxidase deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 06, 2023 | This sequence change creates a premature translational stop signal (p.Asn33Metfs*30) in the SUOX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 513 amino acid(s) of the SUOX protein. This variant is present in population databases (rs773937413, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SUOX-related conditions. ClinVar contains an entry for this variant (Variation ID: 529474). This variant disrupts a region of the SUOX protein in which other variant(s) (p.Tyr400*) have been determined to be pathogenic (PMID: 12112661, 23994568, 24938149, 28629418). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at