rs1396310498
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001292063.2(OTOG):c.494C>A(p.Thr165Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000764 in 1,308,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001292063.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.494C>A | p.Thr165Asn | missense_variant | 6/56 | ENST00000399397.6 | NP_001278992.1 | |
OTOG | NM_001277269.2 | c.530C>A | p.Thr177Asn | missense_variant | 5/55 | NP_001264198.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.494C>A | p.Thr165Asn | missense_variant | 6/56 | 5 | NM_001292063.2 | ENSP00000382329 | P2 | |
OTOG | ENST00000399391.7 | c.530C>A | p.Thr177Asn | missense_variant | 5/55 | 5 | ENSP00000382323 | A2 | ||
OTOG | ENST00000498332.5 | n.400C>A | non_coding_transcript_exon_variant | 5/16 | 5 | |||||
OTOG | ENST00000428619.1 | downstream_gene_variant | 3 | ENSP00000399057 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000125 AC: 1AN: 80046Hom.: 0 AF XY: 0.0000248 AC XY: 1AN XY: 40370
GnomAD4 exome AF: 7.64e-7 AC: 1AN: 1308186Hom.: 0 Cov.: 32 AF XY: 0.00000157 AC XY: 1AN XY: 635292
GnomAD4 genome Cov.: 33
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 | Jul 25, 2017 | The p.Thr177Asn variant in OTOG has not been previously reported in individuals with hearing loss, but has been identified in 1/11462 of Latino chromosomes by t he Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/). Alth ough this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and co nservation analyses do not provide strong support for or against an impact to th e protein. In summary, the clinical significance of the p.Thr177Asn variant is u ncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 28, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at