rs35010860
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001378609.3(OTOGL):c.6859C>T(p.Pro2287Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,592,074 control chromosomes in the GnomAD database, including 401 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2287L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378609.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.6859C>T | p.Pro2287Ser | missense_variant, splice_region_variant | 58/59 | ENST00000547103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.6859C>T | p.Pro2287Ser | missense_variant, splice_region_variant | 58/59 | 5 | NM_001378609.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0284 AC: 4314AN: 151960Hom.: 216 Cov.: 32
GnomAD3 exomes AF: 0.00749 AC: 1802AN: 240436Hom.: 80 AF XY: 0.00544 AC XY: 709AN XY: 130342
GnomAD4 exome AF: 0.00311 AC: 4476AN: 1439996Hom.: 185 Cov.: 29 AF XY: 0.00268 AC XY: 1921AN XY: 716672
GnomAD4 genome ? AF: 0.0284 AC: 4318AN: 152078Hom.: 216 Cov.: 32 AF XY: 0.0275 AC XY: 2046AN XY: 74330
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Pro2278Ser in exon 57 of OTOGL: This variant is not expected to have clinical si gnificance because it has been identified in 8.8% (387/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs35010860). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 23, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at