ClinVar Miner

Submissions for variant NM_021628.3(ALOXE3):c.1559_1562+3dup

dbSNP: rs552323537
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001569323 SCV001793377 uncertain significance not provided 2021-05-28 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing; however, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 27535533)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003155419 SCV003845053 uncertain significance not specified 2023-02-20 criteria provided, single submitter clinical testing Variant summary: ALOXE3 c.1559_1562+3dupAGAGGTG is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant creates a 5 donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00054 in 250312 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in ALOXE3 causing Lamellar Ichthyosis (0.00054 vs 0.00071), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1559_1562+3dupAGAGGTG in individuals affected with Lamellar Ichthyosis and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites this variant uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001569323 SCV004285489 benign not provided 2023-08-31 criteria provided, single submitter clinical testing

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