rs464696
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_144672.4(OTOA):āc.2353A>Cā(p.Thr785Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,567,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_144672.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOA | NM_144672.4 | c.2353A>C | p.Thr785Pro | missense_variant | 22/29 | ENST00000646100.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOA | ENST00000646100.2 | c.2353A>C | p.Thr785Pro | missense_variant | 22/29 | NM_144672.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00920 AC: 1348AN: 146512Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00271 AC: 3856AN: 1421226Hom.: 0 Cov.: 32 AF XY: 0.00266 AC XY: 1885AN XY: 707592
GnomAD4 genome AF: 0.00928 AC: 1360AN: 146628Hom.: 0 Cov.: 32 AF XY: 0.0108 AC XY: 769AN XY: 71166
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Oct 31, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 04, 2019 | The p.Thr785Pro variant in OTOA is classified as benign because it has been iden tified in 0.9% (139/15388) of East Asian chromosomes by gnomAD (http://gnomad.br oadinstitute.org). Furthermore, the threonine (Thr) at this position is not cons erved across species. Over 10 mammals carry a proline (Pro) at this position. - |
OTOA-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 25, 2024 | The OTOA c.2353A>C variant is predicted to result in the amino acid substitution p.Thr785Pro. This variant was reported along with a second potentially pathogenic variant in four individuals with auditory neuropathy and was classified as uncertain (Table S8, Song et al. 2021. PubMed ID: 34175691). This variant is reported in 0.84% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Autosomal recessive nonsyndromic hearing loss 22 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at