Table 1.
Exonic variants prioritized in the analyzed CRC family. Chromosomal positions, classifications, pedigree segregation, allele frequencies, PHRED-like CADD scores, conservational scores, and the percentage of positive intolerance and deleteriousness scores are summarized for each variant. Respective protein functions derived from Genecards are included [19].
| Gene Name | Variant | Exonic Classification | Pedigree Segregation | Allele Frequency | CADD SCORE |
Conservational Scores | Deleteriousness Scores * (%) | Intolerance Scores (%) | Amino Acid Change | Protein Function | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ExAC | gnomAD NFE | GERP++ | PhyloP | PhastCons | |||||||||
| ADAMTS10 | 19_8670022_C_T | nonsyn SNV | I-2, II-1, II-2, II-4, II-6 | 1.92E-05 | 8.95E-06 | 32 | 5.33 | 7.263 | 1 | 66.67 | 80 | V104M | Connective tissue organization, coagulation, inflammation, arthritis, angiogenesis, cell migration |
| C2orf42 | 2_70387896_G_C | nonsyn SNV | I-2, II-1, II-4, II-6 | . | . | 23.5 | 2.33 | 1.849 | 1 | 83.33 | 60 | S459R | No data available |
| GNA13 | 17_63049685_T_C | nonsyn SNV | I-2, II-1, II-2, II-4 | 2.21E-04 | 3.33E-04 | 22.3 | 5.42 | 3.986 | 1 | 75 | 60 | I149V | GPCR signaling, RhoA regulation pathway |
| PTK7 | 6_43100257_G_A | nonsyn SNV | I-2, II-1, II-2, II-4 | 0 | 0.000 | 25.3 | 4.14 | 4.217 | 1 | 66.67 | 100 | V354M | Wnt signaling pathway, cell adhesion, migration, polarity, proliferation, actin cytoskeleton reorganization, apoptosis |
| RSBN1L | 7_77407669_G_A | nonsyn SNV | I-2, II-1, II-4 | 0 | 0.000 | 35 | 5.94 | 7.575 | 1 | 100 | 80 | R603H | Modulation of chromosome architecture by histone demethylation. |
| TNIP1 | 5_150431736_C_T | nonsyn SNV | I-2, II-1, II-2, II-4 | 1.86E-05 | 0.000 | 19.16 | 5.19 | 4.539 | 0.999 | 66.67 | 60 | E238K | Autoimmunity, tissue homeostasis |
non-syn—non-synonymous; NFE—Non-Finnish European population; PP—predicted passenger. * Deleteriousness scores: Following predictions given by deleteriousness scores were considered as favorable in our analysis: SIFT—Damaging (D); Polyphen2_HumDiv, Polyphen2_HumVar—Probably damaging (D) & Possibly damaging (P); LRT—Deleterious (D); MutationTaster—Disease causing (D) & disease causing automatic (A); MutationAssesor—High (H) & medium (M); FATHMM—Damaging (D); MetaSVM—Damaging (D); MetaLR—Damaging (D); VEST3 ≥ 0.5; PROVEAN—Damaging (D); Reliability Index ≥5.