rs764931529
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS2_Supporting
The NM_001292063.2(OTOG):c.4129C>T(p.Arg1377Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000829 in 1,544,008 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1377H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001292063.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.4129C>T | p.Arg1377Cys | missense_variant | 33/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.4165C>T | p.Arg1389Cys | missense_variant | 32/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.4129C>T | p.Arg1377Cys | missense_variant | 33/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.4165C>T | p.Arg1389Cys | missense_variant | 32/55 | 5 | A2 | ||
OTOG | ENST00000342528.2 | n.1467C>T | non_coding_transcript_exon_variant | 9/22 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152236Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000138 AC: 20AN: 144624Hom.: 0 AF XY: 0.000193 AC XY: 15AN XY: 77814
GnomAD4 exome AF: 0.0000855 AC: 119AN: 1391772Hom.: 2 Cov.: 35 AF XY: 0.000107 AC XY: 73AN XY: 685312
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152236Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 29, 2015 | The p.Arg1389Cys variant in OTOG has not been previously reported in individuals with hearing loss, but has been identified in 0.1% (7/5540) of South Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs764931529). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summar y, the clinical significance of the p.Arg1389Cys variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 31, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at