ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.343G>A (p.Val115Met)

gnomAD frequency: 0.00003  dbSNP: rs183450731
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188164 SCV000241771 uncertain significance not provided 2021-11-24 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Reported previously in the heterozygous state in an individual with sporadic ALS (Huang et al., 2021); This variant is associated with the following publications: (PMID: 33226711)
Labcorp Genetics (formerly Invitae), Labcorp RCV000640468 SCV000762060 uncertain significance Neuronal ceroid lipofuscinosis 7 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 115 of the MFSD8 protein (p.Val115Met). This variant is present in population databases (rs183450731, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with MFSD8-related conditions. ClinVar contains an entry for this variant (Variation ID: 206147). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768269 SCV000898829 uncertain significance Neuronal ceroid lipofuscinosis 7; Macular dystrophy with central cone involvement 2021-03-30 criteria provided, single submitter clinical testing MFSD8 NM_152778.2 exon 5 p.Val115Met (c.343G>A): This variant has not been reported in the literature but is present in 0.1% (20/18868) of East Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/4-128865003-C-T). This variant is present in ClinVar (Variation ID:206147). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Natera, Inc. RCV001828003 SCV002084800 uncertain significance Late-infantile neuronal ceroid lipofuscinosis 2020-02-03 no assertion criteria provided clinical testing

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