chr3-124730489-A-G
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000373.4(UMPS):c.18A>G(p.Ala6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,614,170 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 2 hom. )
Consequence
UMPS
NM_000373.4 synonymous
NM_000373.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.89
Genes affected
UMPS (HGNC:12563): (uridine monophosphate synthetase) This gene encodes a uridine 5'-monophosphate synthase. The encoded protein is a bifunctional enzyme that catalyzes the final two steps of the de novo pyrimidine biosynthetic pathway. The first reaction is carried out by the N-terminal enzyme orotate phosphoribosyltransferase which converts orotic acid to orotidine-5'-monophosphate. The terminal reaction is carried out by the C-terminal enzyme OMP decarboxylase which converts orotidine-5'-monophosphate to uridine monophosphate. Defects in this gene are the cause of hereditary orotic aciduria. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 3-124730489-A-G is Benign according to our data. Variant chr3-124730489-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 342926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.89 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UMPS | NM_000373.4 | c.18A>G | p.Ala6= | synonymous_variant | 1/6 | ENST00000232607.7 | |
UMPS | NR_033434.2 | n.38A>G | non_coding_transcript_exon_variant | 1/5 | |||
UMPS | NR_033437.2 | n.38A>G | non_coding_transcript_exon_variant | 1/7 | |||
UMPS | XR_001740253.3 | n.38A>G | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UMPS | ENST00000232607.7 | c.18A>G | p.Ala6= | synonymous_variant | 1/6 | 1 | NM_000373.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00164 AC: 249AN: 152202Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000493 AC: 124AN: 251418Hom.: 2 AF XY: 0.000383 AC XY: 52AN XY: 135894
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GnomAD4 exome AF: 0.000159 AC: 232AN: 1461850Hom.: 2 Cov.: 32 AF XY: 0.000160 AC XY: 116AN XY: 727216
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary orotic aciduria, type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 26, 2023 | - - |
Orotic aciduria Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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