ClinVar Miner

Submissions for variant NM_001371596.2(MFSD8):c.115A>T (p.Ile39Phe)

dbSNP: rs201739608
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188187 SCV000241794 uncertain significance not provided 2016-04-28 criteria provided, single submitter clinical testing The I39F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I39F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000458891 SCV000548723 uncertain significance Neuronal ceroid lipofuscinosis 7 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 39 of the MFSD8 protein (p.Ile39Phe). This variant is present in population databases (rs201739608, gnomAD 0.009%). 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: 206167). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002317123 SCV000849542 uncertain significance Inborn genetic diseases 2021-09-17 criteria provided, single submitter clinical testing The c.115A>T (p.I39F) alteration is located in exon 3 (coding exon 2) of the MFSD8 gene. This alteration results from a A to T substitution at nucleotide position 115, causing the isoleucine (I) at amino acid position 39 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002485273 SCV002792885 uncertain significance Neuronal ceroid lipofuscinosis 7; Macular dystrophy with central cone involvement 2021-07-24 criteria provided, single submitter clinical testing
Natera, Inc. RCV001833125 SCV002084810 uncertain significance Late-infantile neuronal ceroid lipofuscinosis 2020-01-31 no assertion criteria provided clinical testing

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