chr12-80219820-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001378609.3(OTOGL):c.242G>A(p.Cys81Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,548,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001378609.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.242G>A | p.Cys81Tyr | missense_variant | Exon 6 of 59 | ENST00000547103.7 | NP_001365538.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.242G>A | p.Cys81Tyr | missense_variant | Exon 6 of 59 | 5 | NM_001378609.3 | ENSP00000447211.2 | ||
OTOGL | ENST00000646859.1 | c.242G>A | p.Cys81Tyr | missense_variant | Exon 11 of 63 | ENSP00000496036.1 | ||||
OTOGL | ENST00000643417.1 | n.902G>A | non_coding_transcript_exon_variant | Exon 9 of 23 |
Frequencies
GnomAD3 genomes AF: 0.0000136 AC: 2AN: 146618Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000461 AC: 1AN: 216742Hom.: 0 AF XY: 0.00000846 AC XY: 1AN XY: 118272
GnomAD4 exome AF: 0.00000143 AC: 2AN: 1401674Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1AN XY: 698988
GnomAD4 genome AF: 0.0000136 AC: 2AN: 146618Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 71234
ClinVar
Submissions by phenotype
not provided Uncertain:1
The p.Cys72Tyr variant in OTOGL has not been previously reported in individuals with hearing loss but has been identified in 0.00098% (1/102300) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at