rs760941023
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001378609.3(OTOGL):c.1396G>T(p.Val466Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000361 in 1,604,814 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/19 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 Uncertain significance (★).
Frequency
Consequence
NM_001378609.3 missense, splice_region
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.1396G>T | p.Val466Leu | missense_variant, splice_region_variant | 15/59 | ENST00000547103.7 | NP_001365538.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.1396G>T | p.Val466Leu | missense_variant, splice_region_variant | 15/59 | 5 | NM_001378609.3 | ENSP00000447211 | P1 | |
OTOGL | ENST00000646859.1 | c.1396G>T | p.Val466Leu | missense_variant, splice_region_variant | 20/63 | ENSP00000496036 | ||||
OTOGL | ENST00000643417.1 | n.2056G>T | splice_region_variant, non_coding_transcript_exon_variant | 18/23 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151832Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245304Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133362
GnomAD4 exome AF: 0.0000385 AC: 56AN: 1452982Hom.: 0 Cov.: 29 AF XY: 0.0000346 AC XY: 25AN XY: 722964
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151832Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74164
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 | Dec 24, 2015 | The p.Val457Leu variant in OTOGL has not been previously reported in individuals with hearing loss, but has been identified in 1/63270 European chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs7 60941023). Although this variant has been seen in the general population, its fr equency is not high enough to rule out a pathogenic role. Computational predict ion tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Val457 Leu variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at