rs200050988
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001378609.3(OTOGL):c.917C>T(p.Pro306Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00139 in 1,597,446 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001378609.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.917C>T | p.Pro306Leu | missense_variant | Exon 10 of 59 | ENST00000547103.7 | NP_001365538.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.917C>T | p.Pro306Leu | missense_variant | Exon 10 of 59 | 5 | NM_001378609.3 | ENSP00000447211.2 | ||
OTOGL | ENST00000646859.1 | c.917C>T | p.Pro306Leu | missense_variant | Exon 15 of 63 | ENSP00000496036.1 | ||||
OTOGL | ENST00000643417.1 | n.1577C>T | non_coding_transcript_exon_variant | Exon 13 of 23 |
Frequencies
GnomAD3 genomes AF: 0.00114 AC: 174AN: 152038Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00124 AC: 287AN: 231908Hom.: 0 AF XY: 0.00128 AC XY: 162AN XY: 126710
GnomAD4 exome AF: 0.00141 AC: 2043AN: 1445290Hom.: 4 Cov.: 32 AF XY: 0.00135 AC XY: 973AN XY: 719222
GnomAD4 genome AF: 0.00114 AC: 174AN: 152156Hom.: 1 Cov.: 32 AF XY: 0.00122 AC XY: 91AN XY: 74388
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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OTOGL: BS2 -
Reported in a patient with hearing loss in published literature (PMID: 34410491); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34410491) -
not specified Benign:1
p.Pro297Leu in exon 9 of OTOGL: This variant is not expected to have clinical si gnificance because it has been identified in 0.5% (28/5238) of Finnish and in 0. 3% (139/53648) of European chromosomes by the Exome Aggregation Consortium (ExAC , http://exac.broadinstitute.org; dbSNP rs200050988). -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
OTOGL-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at