chr2-26476176-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_194248.3(OTOF):c.2818C>T(p.Gln940Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,774 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_194248.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.2818C>T | p.Gln940Ter | stop_gained | 23/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.577C>T | p.Gln193Ter | stop_gained | 6/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.2818C>T | p.Gln940Ter | stop_gained | 23/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.577C>T | p.Gln193Ter | stop_gained | 6/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246898Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134302
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458774Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 725754
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Rare genetic deafness Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 30, 2014 | The Gln940X variant in OTOF has not been previously reported in individuals with hearing loss or in large population studies. This nonsense variant leads to a p remature termination codon at position 940, which is predicted to lead to a trun cated or absent protein. In summary, this variant meets our criteria to be class ified as pathogenic (http://pcpgm.partners.org/LMM). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at