ClinVar Miner

Submissions for variant NM_032861.4(SERAC1):c.262_265dup (p.Gly89fs)

gnomAD frequency: 0.00001  dbSNP: rs797045105
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000190622 SCV000245658 likely pathogenic 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome 2014-09-28 criteria provided, single submitter clinical testing The p.Gly89AlafsX32 variant in SERAC1 has not been previously reported in individuals with disease or in large population studies. This variant is predicted to cause a frameshift, which would alter the protein’s amino acid sequence beginning at position 89 and lead to a premature termination codon 32 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the SERAC1 gene is an established disease mechanism in individuals with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome. In summary, this variant is likely pathogenic for 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome in an autosomal recessive manner, though additional data is required to prove the predicted impact on the gene.
Invitae RCV000190622 SCV003314997 pathogenic 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome 2023-04-24 criteria provided, single submitter clinical testing This premature translational stop signal has been observed in individual(s) with 3-methylglutaconic aciduria (PMID: 33613893). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly89Alafs*32) in the SERAC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SERAC1 are known to be pathogenic (PMID: 22683713). ClinVar contains an entry for this variant (Variation ID: 208610). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.

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