ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.553+1G>A

dbSNP: rs1553950197
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599516 SCV000710725 likely pathogenic not provided 2018-02-23 criteria provided, single submitter clinical testing The c.553+1G>A variant in the MFSD8 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 6. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.553+1G>A variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.553+1G>A as a likely pathogenic variant.
CeGaT Center for Human Genetics Tuebingen RCV000599516 SCV004151103 pathogenic not provided 2023-10-01 criteria provided, single submitter clinical testing MFSD8: PVS1, PM2
Labcorp Genetics (formerly Invitae), Labcorp RCV003600384 SCV004529527 likely pathogenic Neuronal ceroid lipofuscinosis 7 2023-06-18 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 504403). This variant has not been reported in the literature in individuals affected with MFSD8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 of the MFSD8 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MFSD8 are known to be pathogenic (PMID: 19177532, 25227500, 28586915). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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