ClinVar Miner

Submissions for variant NM_000533.5(PLP1):c.4+4A>C

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002375660 SCV002624455 uncertain significance Inborn genetic diseases 2016-04-11 criteria provided, single submitter clinical testing The c.4+4A>C intronic variant results from an A to C substitution 4 nucleotides after coding exon 1 in the PLP1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003102498 SCV003474993 uncertain significance Hereditary spastic paraplegia 2 2022-11-08 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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. Variants that disrupt 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 is not likely to affect RNA splicing. This variant has not been reported in the literature in individuals affected with PLP1-related conditions. This sequence change falls in intron 1 of the PLP1 gene. It does not directly change the encoded amino acid sequence of the PLP1 protein. It affects a nucleotide within the consensus splice site.

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