rs1555971000
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_001407092.1(OTC):c.-79-63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
OTC
NM_001407092.1 intron
NM_001407092.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.21
Genes affected
OTC (HGNC:8512): (ornithine transcarbamylase) This nuclear gene encodes a mitochondrial matrix enzyme. The encoded protein is involved in the urea cycle which functions to detoxify ammonia into urea for excretion. Mutations in this enzyme lead to ornithine transcarbamylase deficiency, which causes hyperammonemia. [provided by RefSeq, May 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-38352555-G-A is Pathogenic according to our data. Variant chrX-38352555-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 487342.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTC | NM_001407092.1 | c.-79-63G>A | intron_variant | ||||
OTC | NM_000531.6 | upstream_gene_variant | ENST00000039007.5 | ||||
OTC | XM_017029556.2 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTC | ENST00000039007.5 | upstream_gene_variant | 1 | NM_000531.6 | P1 | ||||
OTC | ENST00000488812.1 | upstream_gene_variant | 5 | ||||||
OTC | ENST00000643344.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 5
GnomAD4 exome
Cov.:
5
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ornithine carbamoyltransferase deficiency Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 06, 2019 | 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. Experimental studies have shown that this promoter change causes a reduction of OTC transcription (PMID: 29282796). This variant has been observed in individuals affected with clinical features of OTC deficiency (PMID: 29282796, Invitae). ClinVar contains an entry for this variant (Variation ID: 487342). This variant is not present in population databases (ExAC no frequency). This variant occurs in a non-coding region of the OTC gene. It does not change the encoded amino acid sequence of the OTC protein. - |
Likely pathogenic, no assertion criteria provided | research | Caldovic Lab, Children's National Health System | Dec 12, 2017 | The patient had clinical and biochemical symptoms of OTC deficiency, and no disease causing sequence variants in the OTC coding sequence and canonical splice sites. Functional testing in cultured cells indicates reduced expression of reporter gene - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at