chr3-124730597-C-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_000373.4(UMPS):c.126C>A(p.Gly42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,612,234 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 0.00053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )
Consequence
UMPS
NM_000373.4 synonymous
NM_000373.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.169
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 Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
Variant 3-124730597-C-A is Benign according to our data. Variant chr3-124730597-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 501885.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.169 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UMPS | NM_000373.4 | c.126C>A | p.Gly42= | synonymous_variant | 1/6 | ENST00000232607.7 | |
UMPS | NR_033434.2 | n.146C>A | non_coding_transcript_exon_variant | 1/5 | |||
UMPS | NR_033437.2 | n.146C>A | non_coding_transcript_exon_variant | 1/7 | |||
UMPS | XR_001740253.3 | n.146C>A | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UMPS | ENST00000232607.7 | c.126C>A | p.Gly42= | synonymous_variant | 1/6 | 1 | NM_000373.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000526 AC: 80AN: 152136Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000112 AC: 28AN: 250990Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135658
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GnomAD4 exome AF: 0.0000616 AC: 90AN: 1459980Hom.: 0 Cov.: 33 AF XY: 0.0000358 AC XY: 26AN XY: 725888
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GnomAD4 genome AF: 0.000525 AC: 80AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74464
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 08, 2017 | - - |
UMPS-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 02, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary orotic aciduria, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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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