ClinVar Miner

Submissions for variant NM_001128126.3(AP4S1):c.2T>C (p.Met1Thr)

dbSNP: rs755820725
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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 RCV000624520 SCV000741059 likely pathogenic Inborn genetic diseases 2015-11-09 criteria provided, single submitter clinical testing
Invitae RCV002532827 SCV003016381 likely pathogenic Spastic paraplegia 2023-04-24 criteria provided, single submitter clinical testing 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. This variant disrupts a region of the AP4S1 protein in which other variant(s) (p.Leu6Pro) have been observed in individuals with AP4S1-related conditions (PMID: 32979048). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 520786). Disruption of the initiator codon has been observed in individual(s) with clinical features of hereditary spastic paraplegia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change affects the initiator methionine of the AP4S1 mRNA. The next in-frame methionine is located at codon 7.

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