rs121908609
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM4PP5_Moderate
The NM_004531.5(MOCS2):āc.567A>Cā(p.Ter189TyrextTer18) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,612,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000015 ( 0 hom. )
Consequence
MOCS2
NM_004531.5 stop_lost
NM_004531.5 stop_lost
Scores
1
6
Clinical Significance
Conservation
PhyloP100: 1.73
Genes affected
MOCS2 (HGNC:7193): (molybdenum cofactor synthesis 2) Eukaryotic molybdoenzymes use a unique molybdenum cofactor (MoCo) consisting of a pterin, termed molybdopterin, and the catalytically active metal molybdenum. MoCo is synthesized from precursor Z by the heterodimeric enzyme molybdopterin synthase. The large and small subunits of molybdopterin synthase are both encoded from this gene by overlapping open reading frames. The proteins were initially thought to be encoded from a bicistronic transcript. They are now thought to be encoded from monocistronic transcripts. Alternatively spliced transcripts have been found for this locus that encode the large and small subunits. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Stoplost variant in NM_004531.5 Downstream stopcodon found after 21 codons.
PP5
?
Variant 5-53098602-T-G is Pathogenic according to our data. Variant chr5-53098602-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 6115.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-53098602-T-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MOCS2 | NM_004531.5 | c.567A>C | p.Ter189TyrextTer18 | stop_lost | 7/7 | ENST00000396954.8 | |
MOCS2 | NM_176806.4 | c.*487A>C | 3_prime_UTR_variant | 7/7 | ENST00000450852.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MOCS2 | ENST00000396954.8 | c.567A>C | p.Ter189TyrextTer18 | stop_lost | 7/7 | 1 | NM_004531.5 | P1 | |
MOCS2 | ENST00000450852.8 | c.*487A>C | 3_prime_UTR_variant | 7/7 | 1 | NM_176806.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251248Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135814
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1460578Hom.: 0 Cov.: 29 AF XY: 0.0000165 AC XY: 12AN XY: 726682
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2023 | This sequence change disrupts the translational stop signal of the MOCS2B mRNA. It is expected to extend the length of the MOCS2B protein by 18 additional amino acid residues. This variant is present in population databases (rs121908609, gnomAD 0.05%). This protein extension has been observed in individual(s) with clinical features of molybdenum cofactor deficiency (PMID: 16021469; Invitae). This variant is also known as X189Y. ClinVar contains an entry for this variant (Variation ID: 6115). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this protein extension affects MOCS2B function (PMID: 16021469). 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. - |
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2005 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MutationTaster
Benign
A;A;A;A;A;A;A
Vest4
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at