Table 1.

Main characteristics of the PSMC3 de novo variants^¥ identified in the patients included in the study.

Chromosomal localization (Chr11/GRCh37)	cDNA change ¶	Protein change	Variant database †	CADD Phred score (v1.6.)	Meta-dome	Mobi-Details ‡	Effect on neuronal development	Effect on PSMC3 stability	Effect on proteasome assembly	Effect on mitophagy	IFN signature	Number of patientss with the variant
g.47445677G>A	c.511C>T	R171W	rs775517283	27.3	I	45364	improvement	Decrease	ND	ND	ND	1
g.47445665T>C	c.523A>G	M175V	Absent	23.4	I	45365	ND	none	ND	ND	ND	1
g.47444430G>A	c.686C>T	P229L	Absent	25.5	I	195979	ND	ND	ND	ND	ND	1
g.47444406G>A	c.710C>T	A237V	Absent	26.9	HI	45366	ND	Decrease	ND	ND	ND	1
g.47444234T>C	c.775A>G	M259V	Absent	23.4	I	45367	ND	none	ND	ND	ND	1
g.47444233A>G	c.776T>C	M259T	Absent	24.7	I	45368	ND	Decrease	ND	ND	ND	1
g.47444227A>G	c.782T>C	I261T	Absent	24.6	I	45369	ND	Decrease	ND	ND	ND	6
g.47444225C>T	c.784G>A	G262R	Absent	26.8	I	45370	ND	none	none	increase	moderate	1
g.47444203C>G	c.806G>C	R269P	Absent	24	I	45371	ND	Decrease	ND			1
g.47444150C>G	c.859G>C	E287Q	Absent	26.7	I	45372	ND	Decrease	ND			1
g.47442253G>A	c.910C>T	R304W	rs1363348500	31	I	45373	impairment	none	impairment	increase	strong/very strong	4
g.47442253G>C	c.910C>G	R304G	Absent	28.2	I	45374	ND	none	ND			1
g.47442248C>A	c.915G>T	E305D	Absent	23.1	I	45375	impairment	none	impairment	increase	moderate	1
g.47442234A>G	c.929T>C	M310T	Absent	26.2	HI	45376	ND	none	ND			1
g.47440729C>T	c.1147G>A	E383K	Absent	27.8	N	45377	impairment	none	ND			1

^¥All variants presented are de novo, except variant c.775A>G that is suspected de novo.

^¶RefSeq transcript used for PSMC3 is NM_002804.4; ^† gnomAD V3, dbSNP v154, ClinVar v20210828; ^‡ The access to detailed predictions for variant XXXXX (5364, 45365…) is as follows: https://mobidetails.iurc.montp.inserm.fr/MD/api/variant/XXXXX/browser/

ND: not determined; IFN: interferon; Metadome: I= intolerent; HI= highly intolerent; N= neutral