Unraveling the complex genetic landscape of OTOF-related hearing loss: a deep dive into cryptic variants and haplotype phasing

Table 4 Comparison between OTOF c.5975A > G (p.Lys1992Arg) and c.5098G > C (p.Glu1700Gln)

	c.5975A > G (p.Lys1992Arg)	c.5098G > C (p.Glu1700Gln)
Allele frequencies
Grpmax-AF (gnomAD)^a	0.0008018 (16/19954)	0.0068 (135/19930)
Individuals with homozygote^b	0/9977 (EAS)	1/9965 (EAS)
TB-MAF (Taiwan Biobank)^c	0.002 (6/1513)	0.0073 (22/1516)
Conservation prediction
phyloP100way	7.871	7.619
Pathogenicity prediction
SIFT	0.346 (T)	0.058 (T)
PolyPhen-2-HDIV	1 (D)	0.996 (D)
PolyPhen-2-HVAR	0.997 (D)	0.898 (PD)
MutationTaster	1 (D)	1 (D)
FATHMM-MKL	0.98321 (D)	0.98954 (D)
CADD	21.6	32
DANN	0.999	0.998
Pathogenicity assertions^d	PM2_P, PM3_VS, PP1_S, PP3, PP4 【Pathogenic】 (This study)	PM3_VS, PP1_S, PP3, PP4 【Pathogenic】 (By ClinGen)

Abbreviations: D Damaging, T Tolerant
^aLast accessed on gnomAD (ver. 2.1.1) on August 10, 2024. (allele number in parentheses)
^bThe number of homozygotes in the selected subpopulation with the maximal allele frequency (Grpmax-AF) in gnomAD (ver. 2.1.1). EAS: East Asian
^cLast accessed at Taiwan Biobank on August 10, 2024. (allele number in parentheses)
^dThe criteria and variant classification of each variant were made according to the ClinGen expert-specified ACMG guidelines (Richards et al. 2015; Oza et al. 2018). VS: very strong; S: strong; P: supporting

ISSN: 1528-3658