ClinVar Miner

Submissions for variant NM_001253852.3(AP4B1):c.1244G>A (p.Cys415Tyr)

gnomAD frequency: 0.00028  dbSNP: rs200590674
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV001507969 SCV001713835 uncertain significance not provided 2020-09-10 criteria provided, single submitter clinical testing
GeneDx RCV001507969 SCV001999201 uncertain significance not provided 2019-10-22 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002567983 SCV002949034 uncertain significance Hereditary spastic paraplegia 47 2022-05-05 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 415 of the AP4B1 protein (p.Cys415Tyr). This variant is present in population databases (rs200590674, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with AP4B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1163150). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002564221 SCV003629592 uncertain significance Inborn genetic diseases 2021-06-04 criteria provided, single submitter clinical testing The c.1244G>A (p.C415Y) alteration is located in exon 8 (coding exon 7) of the AP4B1 gene. This alteration results from a G to A substitution at nucleotide position 1244, causing the cysteine (C) at amino acid position 415 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV002567983 SCV004050656 uncertain significance Hereditary spastic paraplegia 47 2023-04-11 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV001507969 SCV005186827 uncertain significance not provided criteria provided, single submitter not provided

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