ClinVar Miner

Submissions for variant NM_138773.4(SLC25A46):c.620+4_620+7del

dbSNP: rs1580866253
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795296 SCV000934751 uncertain significance Neuropathy, hereditary motor and sensory, type 6B 2022-04-01 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the SLC25A46 gene. It does not directly change the encoded amino acid sequence of the SLC25A46 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC25A46-related conditions. ClinVar contains an entry for this variant (Variation ID: 641936). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV004818034 SCV005438746 uncertain significance Pontocerebellar hypoplasia, type 1E 2023-07-22 criteria provided, single submitter clinical testing The observed splice donor c.620+4_620+7del variant in SLC25A46 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency of 0% in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. The variant affects the GT donor splice site downstream of exon 6. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. However, since this variant is present in the penultimate intron, functional studies will be required to prove protein truncation. The spliceAI tool predicts that this splice site variant is damaging. For these reasons, this variant has been classified as Uncertain Significance.

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