ClinVar Miner

Submissions for variant NM_001875.5(CPS1):c.4161G>A (p.Lys1387=)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002995699 SCV003298123 uncertain significance Congenital hyperammonemia, type I 2021-05-04 criteria provided, single submitter clinical testing This sequence change affects codon 1387 of the CPS1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CPS1 protein. This variant also falls at the last nucleotide of exon 35, which is part of the consensus splice site for this exon. This variant is present in population databases (rs200616712, ExAC 0.03%). This variant has not been reported in the literature in individuals with CPS1-related conditions. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
GeneDx RCV004593116 SCV005080414 uncertain significance not provided 2023-12-10 criteria provided, single submitter clinical testing Variant at the last nucleotide of the exon in a gene for which loss of function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge
3billion, Medical Genetics RCV002995699 SCV005328983 likely benign Congenital hyperammonemia, type I 2024-09-20 criteria provided, single submitter clinical testing The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant.

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