chr12-56004183-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001032386.2(SUOX):c.794C>A(p.Ala265Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A265T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001032386.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUOX | NM_001032386.2 | c.794C>A | p.Ala265Asp | missense_variant | 5/5 | ENST00000266971.8 | |
SUOX | NM_000456.3 | c.794C>A | p.Ala265Asp | missense_variant | 6/6 | ||
SUOX | NM_001032387.2 | c.794C>A | p.Ala265Asp | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUOX | ENST00000266971.8 | c.794C>A | p.Ala265Asp | missense_variant | 5/5 | 2 | NM_001032386.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461876Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 727240
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Sulfite oxidase deficiency Pathogenic:1Uncertain:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 15, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been observed in individual(s) with sulfite oxidase deficiency (PMID: 10519592, 9428520). This variant is also known as c.623C>A (p.Ala208Asp). ClinVar contains an entry for this variant (Variation ID: 3821). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with aspartic acid at codon 265 of the SUOX protein (p.Ala265Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 26, 1997 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at