Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015122.3(FCHO1):c.33G>T(p.Glu11Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
FCHO1 (HGNC:29002): (FCH and mu domain containing endocytic adaptor 1) Enables AP-2 adaptor complex binding activity. Involved in clathrin coat assembly and clathrin-dependent endocytosis. Located in cytosol; nucleoplasm; and plasma membrane. Is active in clathrin-coated pit. Implicated in primary immunodeficiency disease. [provided by Alliance of Genome Resources, Apr 2022]
Uncertain significance, criteria provided, single submitter
clinical testing
Invitae
Dec 31, 2023
This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 11 of the FCHO1 protein (p.Glu11Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FCHO1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. -
Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);Gain of ubiquitination at K12 (P = 0.1047);.;