ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.863+1G>A (rs200319160)

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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, Partners HealthCare Personalized Medicine RCV000616705 SCV000711766 pathogenic Late-infantile neuronal ceroid lipofuscinosis 2016-02-19 criteria provided, single submitter clinical testing The c.863+1G>A variant in MFSD8 has not been previously reported in individuals with late-infantile neuronal ceroid lipofuscinosis and was absent from large pop ulation studies. This variant occurs in the invariant region (+/- 1,2) of the sp lice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. In summary, this variant meets our criteria to be c lassified as pathogenic for late-infantile neuronal ceroid lipofuscinosis in an autosomal recessive manner.
Invitae RCV001067482 SCV001232548 pathogenic Neuronal ceroid lipofuscinosis 7 2019-02-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the MFSD8 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in several individuals affected with MFSD8-related conditions (PMID: 28600779, 19177532). ClinVar contains an entry for this variant (Variation ID: 504888). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants 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). For these reasons, this variant has been classified as Pathogenic.

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