rs369473810
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001378609.3(OTOGL):āc.214T>Cā(p.Trp72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,552,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001378609.3 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 |
---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.214T>C | p.Trp72Arg | missense_variant | 5/59 | ENST00000547103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.214T>C | p.Trp72Arg | missense_variant | 5/59 | 5 | NM_001378609.3 | P1 | |
OTOGL | ENST00000646859.1 | c.214T>C | p.Trp72Arg | missense_variant | 10/63 | ||||
OTOGL | ENST00000643417.1 | n.874T>C | non_coding_transcript_exon_variant | 8/23 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000417 AC: 8AN: 191844Hom.: 0 AF XY: 0.0000193 AC XY: 2AN XY: 103512
GnomAD4 exome AF: 0.0000129 AC: 18AN: 1400716Hom.: 0 Cov.: 29 AF XY: 0.0000144 AC XY: 10AN XY: 695102
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74360
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 | Aug 31, 2016 | The p.Trp63Arg variant in OTOGL has not been previously reported in individuals with hearing loss, and has been identified in 1/1188 Latino chromosomes by the E xome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs36947 3810). Although this variant has been seen in the general population, its frequ ency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Trp63Arg v ariant is uncertain. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.187T>C (p.W63R) alteration is located in exon 4 (coding exon 4) of the OTOGL gene. This alteration results from a T to C substitution at nucleotide position 187, causing the tryptophan (W) at amino acid position 63 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at