ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.576C>G (p.Phe192Leu)

gnomAD frequency: 0.00010  dbSNP: rs777020801
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002317574 SCV000851097 uncertain significance Inborn genetic diseases 2016-06-24 criteria provided, single submitter clinical testing The p.F192L variant (also known as c.576C>G), located in coding exon 6 of the MFSD8 gene, results from a C to G substitution at nucleotide position 576. The phenylalanine at codon 192 is replaced by leucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000803180 SCV000943042 uncertain significance Neuronal ceroid lipofuscinosis 7 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 192 of the MFSD8 protein (p.Phe192Leu). This variant is present in population databases (rs777020801, gnomAD 0.01%). 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: 589864). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MFSD8 protein function. 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.
GeneDx RCV001585682 SCV001818043 uncertain significance not provided 2020-01-03 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001825441 SCV002084793 uncertain significance Late-infantile neuronal ceroid lipofuscinosis 2019-11-11 no assertion criteria provided clinical testing

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