6-39912289-C-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_001358530.2(MOCS1):c.956G>A(p.Arg319Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,018 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 Likely pathogenic (★★).
Frequency
Consequence
NM_001358530.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MOCS1 | NM_001358530.2 | c.956G>A | p.Arg319Gln | missense_variant | Exon 8 of 11 | ENST00000340692.10 | NP_001345459.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251476Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135912
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1460830Hom.: 0 Cov.: 31 AF XY: 0.0000427 AC XY: 31AN XY: 726726
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A Pathogenic:3
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This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 319 of the MOCS1 protein (p.Arg319Gln). This variant is present in population databases (rs104893969, gnomAD 0.02%). This missense change has been observed in individuals with molybdenum cofactor deficiency (PMID: 9921896, 35192225). ClinVar contains an entry for this variant (Variation ID: 6119). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
MOCS1-related disorder Pathogenic:1
The MOCS1 c.956G>A variant is predicted to result in the amino acid substitution p.Arg319Gln. This variant has been reported in the homozygous and presumed compound heterozygous states in individuals with molybdenum cofactor deficiency (Reiss et al. 1998. PubMed ID: 9921896). In one study of MoCo-deficient patients, this variant was identified in 15% of the patients tested (Reiss et al. 1998. PubMed ID: 9921896). This variant is reported in 0.023% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-39880033-C-T) and it reported as pathogenic/likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/6119/). This variant is interpreted as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at