In AK368692, one variant was located upstream to the coding region and in AK362742 two variants were synonymous substitutions.
46 of the exonic variants were synonymous changes (32 in TERT and 9 in CLPTM1L) and 26 were non-synonymous protein altering variants (PAV) (17 in TERT and 9 in CLPTM1L).
> -wrap-foot> Thexpecteded percentage of de novo variants in coding or splicing sequence that are synonymous is 29% (12), however, we observed that only three (9%) of the 33 validated independent de novo variants were synonymous, with 26 being non-synonymous, three nonsense and one in a splice site.
Five were intronic (not splice site) variants, three were synonymous and five were non-synonymous variants.
In addition, 6 of the 15 novel, non-haplogroup-associated variants were nonsynonymous variants and 9 were synonymous variants.
Of the 11 coding variants, 10 were synonymous (nine known, one novel) and one was a rare missense variant (MAF = 0.007), rs148064770 (present), present as a heterozygous allele in one of the CEU SZ probands.
Of these five variants, three were synonymous changes (L18L, S192S, P394P), and two resulted in non-conservative changes (T134M, L347R) in evolutionary conserved amino acids (Fig. 1B, C).
Within the total set of 9,665,340 identified SNVs, 67,616 were in protein-coding sequence, among which 29,131 were nonsynonymous coding (NSC) variants and 38,485 were synonymous coding (SC) variants.
Of the 22 exonic variants, two were nonsense mutations resulting in predicted stop codons (PALB2 c.196C>T, p.Gln66*; PALB2 c.3113G>A, p.Trp1038*), two were frameshift mutations resulting in premature termination codons (PTC; PALB2 c.1947_1948insA, p.Glu650fs*13; p.Ala995fs*162983insT, p.Ala995fs*10), 10 were missense variants, and the remaining eight were synonymous variants.
Our thorough screening of NuMA gene in breast cancer cases resulted in identification of several variants of which eight were missense changes and the rest were synonymous variants or not located in coding regions.
Of the twenty-three likely benign variants five were intronic, 13 were synonymous and 5 were missense variants.
