ClinVar Miner

Submissions for variant NM_007289.4(MME):c.2154-5_2160del

dbSNP: rs1712962174
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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 RCV001900733 SCV002144235 uncertain significance not provided 2021-07-13 criteria provided, single submitter clinical testing This variant results in the deletion of part of exon 23 (c.2154-5_2160del) of the MME gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MME-related conditions. Nucleotide substitutions within 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.
Ambry Genetics RCV003164231 SCV003887361 uncertain significance Inborn genetic diseases 2023-01-09 criteria provided, single submitter clinical testing The c.2154-5_2160del12 alteration consists of a deletion of 12 nucleotides from nucleotide positions c.2154-5 to c.2160 and involves the canonical splice acceptor site before exon 23 (coding exon 22) of the MME gene. This alteration occurs at the 3' terminus of the MME gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 4% of the protein. The exact functional effect of this alteration is unknown. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This canonical acceptor site is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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