X-38352555-G-A
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
Consequence
NM_001407092.1 intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTC | NM_001407092.1 | c.-79-63G>A | intron_variant | Intron 2 of 11 | NP_001394021.1 | |||
OTC | NM_000531.6 | c.-142G>A | upstream_gene_variant | ENST00000039007.5 | NP_000522.3 | |||
OTC | XM_017029556.2 | c.-142G>A | upstream_gene_variant | XP_016885045.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENSG00000250349 | ENST00000465127.1 | c.172-313566G>A | intron_variant | Intron 3 of 8 | 5 | ENSP00000417050.1 | ||||
OTC | ENST00000039007.5 | c.-142G>A | upstream_gene_variant | 1 | NM_000531.6 | ENSP00000039007.4 | ||||
OTC | ENST00000488812.1 | n.-50G>A | upstream_gene_variant | 5 | ||||||
OTC | ENST00000643344.1 | n.-142G>A | upstream_gene_variant | ENSP00000496606.1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 5
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Ornithine carbamoyltransferase deficiency Pathogenic:2
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 -
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. This variant is not present in population databases (ExAC no frequency). 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). Experimental studies have shown that this promoter change causes a reduction of OTC transcription (PMID: 29282796). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at