18-36187535-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_017947.4(MOCOS):c.-5G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,235,088 control chromosomes in the GnomAD database, including 3,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.054 ( 327 hom., cov: 34)
Exomes 𝑓: 0.076 ( 3316 hom. )
Consequence
MOCOS
NM_017947.4 5_prime_UTR
NM_017947.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.693
Genes affected
MOCOS (HGNC:18234): (molybdenum cofactor sulfurase) This gene encodes an enzyme that sulfurates the molybdenum cofactor which is required for activation of the xanthine dehydrogenase (XDH) and aldehyde oxidase (AO) enzymes. XDH catalyzes the conversion of hypoxanthine to uric acid via xanthine, as well as the conversion of allopurinol to oxypurinol, and pyrazinamide to 5-hydroxy pyrazinamide. Mutations in this gene cause the metabolic disorder classical xanthinuria type II which is characterized by the loss of XDH/XO and AO enzyme activity, decreased levels of uric acid in the urine, increased levels of xanthine and hypoxanthine in the serum and urine, formation of xanthine stones in the urinary tract, and myositis due to tissue deposition of xanthine. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 18-36187535-G-A is Benign according to our data. Variant chr18-36187535-G-A is described in ClinVar as [Benign]. Clinvar id is 1296803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MOCOS | NM_017947.4 | c.-5G>A | 5_prime_UTR_variant | 1/15 | ENST00000261326.6 | NP_060417.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MOCOS | ENST00000261326.6 | c.-5G>A | 5_prime_UTR_variant | 1/15 | 1 | NM_017947.4 | ENSP00000261326 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0537 AC: 8176AN: 152138Hom.: 327 Cov.: 34
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GnomAD3 exomes AF: 0.0761 AC: 673AN: 8846Hom.: 31 AF XY: 0.0761 AC XY: 375AN XY: 4926
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GnomAD4 exome AF: 0.0758 AC: 82093AN: 1082838Hom.: 3316 Cov.: 34 AF XY: 0.0758 AC XY: 38844AN XY: 512262
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GnomAD4 genome AF: 0.0537 AC: 8173AN: 152250Hom.: 327 Cov.: 34 AF XY: 0.0535 AC XY: 3982AN XY: 74430
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
MOCOS-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 05, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at