chr12-80210862-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001378609.3(OTOGL):c.95C>T(p.Ser32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,472,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S32S) has been classified as Likely benign.
Frequency
Consequence
NM_001378609.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.95C>T | p.Ser32Leu | missense_variant | 3/59 | ENST00000547103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.95C>T | p.Ser32Leu | missense_variant | 3/59 | 5 | NM_001378609.3 | P1 | |
OTOGL | ENST00000646859.1 | c.95C>T | p.Ser32Leu | missense_variant | 8/63 | ||||
OTOGL | ENST00000643417.1 | n.755C>T | non_coding_transcript_exon_variant | 6/23 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 151692Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000127 AC: 14AN: 109812Hom.: 0 AF XY: 0.0000991 AC XY: 6AN XY: 60540
GnomAD4 exome AF: 0.000210 AC: 277AN: 1320688Hom.: 0 Cov.: 28 AF XY: 0.000198 AC XY: 129AN XY: 651976
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 151692Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74040
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 23 of the OTOGL protein (p.Ser23Leu). This variant is present in population databases (rs760011677, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with OTOGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1519086). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2023 | The c.68C>T (p.S23L) alteration is located in exon 2 (coding exon 2) of the OTOGL gene. This alteration results from a C to T substitution at nucleotide position 68, causing the serine (S) at amino acid position 23 to be replaced by a leucine (L). 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