I had this configuration in a server
/etc/network/interfaces
auto em1
iface em1 inet static
   address 192.168.1.250
   network 192.168.1.0
   netmask 255.255.255.0
   broadcast 192.168.1.255
   gateway 192.168.1.1
/etc/NetworkManager/system-connections/wired-conexion
[connection]
id=wired-conexion
uuid=0c501f08acc5497cb7de8c815a297537
type=8023ethernet
[8023ethernet]
[ipv4]
method=manual
dns=8.8.8.8;
dns-search=8.8.4.4;
address1=192.168.1.250/24,192.168.1.1
[ipv6]
method=auto
ip6privacy=0
Then I commented these lines in /etc/network/interfaces file
# auto em1
# iface em1 inet static
#    address 192.168.1.250
#    network 192.168.1.0
#    netmask 255.255.255.0
#    broadcast 192.168.1.255
#    gateway 192.168.1.1
I restarted the service
service network-manager restart
And I lost the communication with the server because I was remotely connected. I have a similar configuration in my  laptop and everything works well. I thought the file /etc/network/interfaces was ignored when I used the network-manager, is that right? If I uncomment again the lines will it work again?
Update: more configurations (I change manage -> true) and /etc/network/interfaces should be ignored
/etc/NetworkManager/system-connections/conexionname
[connection]
id=conexionname
uuid=8e603a9b-...
type=802-3-ethernet
[802-3-ethernet]
[ipv4]
method=manual
dns=8.8.8.8;
dns-search=8.8.4.4;
address1=192.168.1.250/24,192.168.1.1
may-fail=false
[ipv6]
method=auto
ip6-privacy=0
/etc/NetworkManager/NetworkManager.conf
[main]
plugins=ifupdown,keyfile,ofono
dns=dnsmasq
[ifupdown]
managed=true
 
    