ClinVar Miner

Submissions for variant NM_004208.4(AIFM1):c.1465G>A (p.Asp489Asn)

gnomAD frequency: 0.00002  dbSNP: rs748493176
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001208296 SCV001379676 uncertain significance Charcot-Marie-Tooth Neuropathy X; Combined oxidative phosphorylation deficiency 2021-06-11 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with AIFM1-related conditions. This variant is present in population databases (rs748493176, ExAC 0.01%). This sequence change replaces aspartic acid with asparagine at codon 489 of the AIFM1 protein (p.Asp489Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine.
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin RCV002285022 SCV002574874 uncertain significance not specified 2022-09-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002562343 SCV003720756 uncertain significance Inborn genetic diseases 2021-12-14 criteria provided, single submitter clinical testing The c.1465G>A (p.D489N) alteration is located in exon 14 (coding exon 14) of the AIFM1 gene. This alteration results from a G to A substitution at nucleotide position 1465, causing the aspartic acid (D) at amino acid position 489 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003327494 SCV004034738 uncertain significance not provided 2023-09-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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