Submissions for variant NM_001358530.2(MOCS1):c.1150G>A (p.Glu384Lys)

gnomAD frequency: 0.00001  dbSNP: rs751603831

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000642133	SCV000763786	uncertain significance	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	2022-08-10	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 384 of the MOCS1 protein (p.Gly384Ser). This variant is present in population databases (rs751603831, gnomAD 0.007%). This missense change has been observed in individual(s) with molybdenum cofactor deficiency (PMID: 9921896). ClinVar contains an entry for this variant (Variation ID: 534542). 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 C0"). Experimental studies have shown that this missense change affects MOCS1 function (PMID: 11891227). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Illumina Laboratory Services, Illumina	RCV000642133	SCV000916139	uncertain significance	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	2017-09-06	criteria provided, single submitter	clinical testing	The MOCS1 c.1150G>A (p.Gly384Ser) missense variant has been reported in one study and is found in a compound heterozygous state in one individual with molybdenum cofactor deficiency (Reiss et al. 1998). The p.Gly384Ser variant was absent from 50 control chromosomes and is reported at a frequency of 0.000067 in the European (non-Finnish) population of the Genome Aggregation Database, but this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Expression analysis in E. coli found the p.Gly384Ser variant to have significantly reduced activity compared to wildtype (Hänzelmann et al. 2002). The p.Gly384 residue is conserved across mammals, plants, and bacteria (Reiss et al. 1998). Based on the evidence, the p.Gly384Ser variant is classified as a variant of unknown significance but suspicious for pathogenicity for molybdenum cofactor deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV000642133	SCV004101552	uncertain significance	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A		criteria provided, single submitter	clinical testing	The missense variant in c.1150G>A(p.Glu384Lys) in MOCS1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Glu384Lys variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes and has an allele frequency of 0.003203% from gnomAD database. This variant has been reported to the ClinVar database as Uncertain Significance (VUS). The amino acid change p.Glu384Lys in MOCS1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Glu at position 384 is changed to a Lys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS). The above variant has been observed in the spouse.
Baylor Genetics	RCV000642133	SCV004193252	likely pathogenic	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	2023-08-31	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000642133	SCV004236373	uncertain significance	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	2023-07-26	criteria provided, single submitter	clinical testing