Table 1.
Rare A2ML1 Variants Identified in Otitis-Prone Children from UTMB
| Chr12 hg19 Coordinate |
PhyloP 100 wayall |
GERP | Nucleotide Change |
Amino Acid Change |
Variant Type |
C- score |
Deleterious Prediction |
N
EA/ HA NOP |
N
EA/ HA OP |
N OP with Variant |
Ethnic Group |
ExAC MAF European non-Finn |
ExAC MAF Latino |
Fisher’s exact p-value |
ExAC MAF Other |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 8,990,070 | 0.40 | 2.60 | c.763C>T | p.(Gln255*) | stop-gained | 29.2 | MT | 118 | 84 | 1 het | HA | 0/67,708 | 0/11,606 | 0.001 | 0/43,010 |
| 8,991,805 | 1.90 | 3.33 | c.1067C>G | p.(Pro356Arg) | missense | 15.1 | MA, PP2, S | 110 | 100 | 1 het | EA | 0/67,250 | 0/11,464 | 0.001 | 0/42,430 |
| 9,004,573 | 7.19 | 2.72 | c.955G>A | p.(Ala810Thr) | missense | 21.3 | LRT, MA, MT, PP2, S |
138 | 154 | 1 het | HA | 0/67,668 | 0/11,606 | 0.002 | 0/43,010 |
| 9,004,827 | 1.38 | 1.94 | c.2478_2485 dupGGCTAAAT |
p.(Ser829Trpfs*9) | frameshift | NA | MT | 158 | 168 | 2 hom, 1 het |
2 EA, 1 HA |
0/67,630 | 0/11,606 | 3.34×10−14 | 0/42,982 |
| 9,006,810 | −1.01 | −4.26 | c.2677C>T | p.(Arg893*) | stop-gained | 36.0 | MT | 98 | 106 | 1 het | HA | 14/67,236 = 0.0002 |
1/11,590 =0.00009 |
0.021 | 4/41,890 =0.0001 |
| 9,009,825 | 9.44 | 3.73 | c.2914G>T | p.(Glu972*) | stop-gained | 44.0 | MT | 140 | 156 | 1 het | HA | 0/67,694 | 0/11,602 | 0.002 | 2/43,008 =0.00005 |
| 9,009,912 | 2.78 | 1.72 | c.3001C>T | p.(Arg1001Trp) | missense | 16.8 | MA, PP2, S | 140 | 156 | 1 het | EA | 0/67,634 | 0/11,606 | 0.002 | 0/42,974 |
| 9,027,091 | 3.41 | 2.39 | c.4292C>T | p.(Ala1431Val) | missense | 19.6 | MT, PP2, S | 114 | 164 | 1 het | EA | 0/67,654 | 0/11,586 | 0.002 | 0/42,934 |
UTMB, University of Texas Medical Branch Galveston; ExAC, Exome Aggregation Consortium; MAF, minor allele frequency; MT, MutationTaster; MA, MutationAssessor; PP2, PolyPhen2 HDIV; S, SIFT; LRT, likelihood ratio test; ; EA, European-American; HA, Hispanic-American; NOP, non-otitis-prone alleles screened for variant; OP, otitis-prone alleles screened for variant; het, heterozygous; hom, homozygous.
UTMB 1031 is heterozygous for two variants, c.955G>A (p.(Ala810Thr)) and c.2914G>T (p.(Glu972*)).
All listed variants were not identified in NOP UTMB children, in 1,385 UWCMG exome sequences and in 100 genomes from the Singapore Sequencing Malay Project.
Two-sided Fisher exact tests were performed by comparing variant frequency in UTMB OP children of EA/HA descent with the combined frequencies in: UTMB NOP children of EA/HA descent; 1,378 UWCMG exomes of EA/HA descent; and European non-Finnish and Latino alleles in ExAC.
For variants that are not identified in ExAC, number of alleles was based on the total alleles reported for the ExAC variant nearest to the nucleotide at which the A2ML1 variant in the UTMB child occurred. For each variant site listed, coverage in ExAC was 50-95× on average and at least 30× in 90-99% of 60,706 samples.