ClinVar Miner

Submissions for variant NM_001253852.3(AP4B1):c.894T>A (p.Cys298Ter)

gnomAD frequency: 0.00002  dbSNP: rs746462207
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001211765 SCV001383320 pathogenic Hereditary spastic paraplegia 47 2019-06-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys298*) in the AP4B1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in AP4B1 are known to be pathogenic (PMID: 22290197, 24700674, 24781758). This variant has not been reported in the literature in individuals with AP4B1-related conditions. This variant is present in population databases (rs746462207, ExAC 0.006%).
GeneDx RCV003127686 SCV003803280 pathogenic not provided 2025-04-16 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001211765 SCV004021055 pathogenic Hereditary spastic paraplegia 47 2023-06-12 criteria provided, single submitter clinical testing Variant summary: AP4B1 c.894T>A (p.Cys298X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.4e-05 in 251476 control chromosomes. To our knowledge, no occurrence of c.894T>A in individuals affected with Spastic Paraplegia 47, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 . All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV001211765 SCV004050676 pathogenic Hereditary spastic paraplegia 47 2023-04-11 criteria provided, single submitter clinical testing

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