NM_001378609.3:c.39G>A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001378609.3(OTOGL):c.39G>A(p.Trp13*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000139 in 1,362,508 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 Likely pathogenic (★).
Frequency
Consequence
NM_001378609.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.39G>A | p.Trp13* | stop_gained | Exon 2 of 59 | ENST00000547103.7 | NP_001365538.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.39G>A | p.Trp13* | stop_gained | Exon 2 of 59 | 5 | NM_001378609.3 | ENSP00000447211.2 | ||
OTOGL | ENST00000646859.1 | c.39G>A | p.Trp13* | stop_gained | Exon 7 of 63 | ENSP00000496036.1 | ||||
OTOGL | ENST00000643417.1 | n.699G>A | non_coding_transcript_exon_variant | Exon 5 of 23 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000763 AC: 1AN: 131090Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 71468
GnomAD4 exome AF: 0.0000139 AC: 19AN: 1362508Hom.: 0 Cov.: 28 AF XY: 0.0000178 AC XY: 12AN XY: 672434
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Rare genetic deafness Pathogenic:1
The p.Trp4X variant in OTOGL has been identified in a compound heterozygous stat e in 1 individual with hearing loss, who also carried an additional loss-of-func tion variant in OTOGL (LMM data). It has also been identified in 1/6086 African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinsti tute.org; dbSNP rs1191512072), which is low enough to be consistent with a reces sive carrier frequency. This nonsense variant leads to a premature termination c odon at position 4, which is predicted to lead to a truncated or absent protein. Loss of function of the OTOGL gene is an established disease mechanism in autos omal recessive hearing loss. In summary, although additional studies are require d to fully establish its clinical significance, the p.Trp4X variant is likely pa thogenic. ACMG/AMP Criteria applied: PVS1; PM2_Supporting; PM3. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at