"big" is a very relative term, could you provide something more specific?

If you have enough RAM to load all the data in an array, Sort::Key will allow you to sort it easily and probably faster than with any other method:

use Sort::Key::Multi qw(u3_keysort); # u3 stands for 3 unsigned intege
+r keys

my $ix = 0;
my %map_10th = map { $_ => $ix++ } qw(GENE UTR ...);

my @data = ...;
my @sorted = u3_keysort {
               my @key = split /\s+/;
               ($key[0], $key[1], $map_10th{$key[9]})
             } @data;
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If you don't have enough RAM, then try with Sort::External or just with the sort command provided by your OS.