rs1555976710
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_000531.6(OTC):c.956_958delCTC(p.Pro319del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 23)
Consequence
OTC
NM_000531.6 disruptive_inframe_deletion
NM_000531.6 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.61
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]
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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;
PM4
Nonframeshift variant in NON repetitive region in NM_000531.6. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTC | NM_000531.6 | c.956_958delCTC | p.Pro319del | disruptive_inframe_deletion | 9/10 | ENST00000039007.5 | NP_000522.3 | |
OTC | NM_001407092.1 | c.956_958delCTC | p.Pro319del | disruptive_inframe_deletion | 11/12 | NP_001394021.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTC | ENST00000039007.5 | c.956_958delCTC | p.Pro319del | disruptive_inframe_deletion | 9/10 | 1 | NM_000531.6 | ENSP00000039007.4 | ||
ENSG00000250349 | ENST00000465127.1 | c.172-254171_172-254169delCTC | intron_variant | 5 | ENSP00000417050.1 | |||||
OTC | ENST00000643344.1 | n.*706_*708delCTC | non_coding_transcript_exon_variant | 10/11 | ENSP00000496606.1 | |||||
OTC | ENST00000643344.1 | n.*706_*708delCTC | 3_prime_UTR_variant | 10/11 | ENSP00000496606.1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 06, 2017 | - - |
Ornithine carbamoyltransferase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 13, 2019 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has been observed in an individual affected with OTC deficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 521440). This variant is not present in population databases (ExAC no frequency). This variant, c.956_958del, results in the deletion of 1 amino acid(s) of the OTC protein (p.Pro319del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at