ClinVar Miner

Submissions for variant NM_005050.4(ABCD4):c.542+1G>T

gnomAD frequency: 0.00001  dbSNP: rs769364566
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000373583 SCV000329940 pathogenic not provided 2023-02-05 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant expected to result in aberrant splicing with skipping of exon 5 (Coelho et al., 2012); This variant is associated with the following publications: (PMID: 27766264, 22922874, 33729671)
Labcorp Genetics (formerly Invitae), Labcorp RCV000030861 SCV001588728 pathogenic Methylmalonic acidemia with homocystinuria, type cblJ 2020-08-02 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 of the ABCD4 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs769364566, ExAC 0.001%). This variant has been observed in individual(s) with cblJ deficiency (PMID: 22922874). ClinVar contains an entry for this variant (Variation ID: 280107). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 22922874). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ABCD4 are known to be pathogenic (PMID: 22922874). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000030861 SCV000053536 pathogenic Methylmalonic acidemia with homocystinuria, type cblJ 2012-10-01 no assertion criteria provided literature only

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