rs200316862
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001358530.2(MOCS1):c.162G>A(p.Ala54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,612,412 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
MOCS1
NM_001358530.2 synonymous
NM_001358530.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.10
Genes affected
MOCS1 (HGNC:7190): (molybdenum cofactor synthesis 1) Molybdenum cofactor biosynthesis is a conserved pathway leading to the biological activation of molybdenum. The protein encoded by this gene is involved in this pathway. This gene was originally thought to produce a bicistronic mRNA with the potential to produce two proteins (MOCS1A and MOCS1B) from adjacent open reading frames. However, only the first open reading frame (MOCS1A) has been found to encode a protein from the putative bicistronic mRNA, whereas additional splice variants are likely to produce a fusion between the two open reading frames. This gene is defective in patients with molybdenum cofactor deficiency, type A. A related pseudogene has been identified on chromosome 16. [provided by RefSeq, Nov 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant 6-39927417-C-T is Benign according to our data. Variant chr6-39927417-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 534544.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-1.1 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| MOCS1 | NM_001358530.2 | c.162G>A | p.Ala54= | synonymous_variant | 2/11 | ENST00000340692.10 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MOCS1 | ENST00000340692.10 | c.162G>A | p.Ala54= | synonymous_variant | 2/11 | 5 | NM_001358530.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152158Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000484 AC: 12AN: 247684Hom.: 0 AF XY: 0.0000595 AC XY: 8AN XY: 134538
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GnomAD4 exome AF: 0.000118 AC: 173AN: 1460136Hom.: 0 Cov.: 30 AF XY: 0.000113 AC XY: 82AN XY: 726294
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152276Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9AN XY: 74438
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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