rs774797627
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001378609.3(OTOGL):āc.2945A>Cā(p.Asp982Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000622 in 1,511,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001378609.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.2945A>C | p.Asp982Ala | missense_variant | 27/59 | ENST00000547103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.2945A>C | p.Asp982Ala | missense_variant | 27/59 | 5 | NM_001378609.3 | P1 | |
OTOGL | ENST00000646859.1 | c.2929-5791A>C | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000286 AC: 4AN: 139802Hom.: 0 AF XY: 0.0000402 AC XY: 3AN XY: 74660
GnomAD4 exome AF: 0.0000625 AC: 85AN: 1359642Hom.: 0 Cov.: 29 AF XY: 0.0000551 AC XY: 37AN XY: 671122
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74356
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 04, 2016 | Variant classified as Uncertain Significance - Favor Benign. The p.Asp973Ala var iant in OTOGL has not been previously reported in individuals with hearing loss, but has been identified in 2/54860 European chromosomes by the Genome Aggregati on Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs774797627). Aspar tate (Asp) at position 973 is not conserved in mammals or evolutionarily distant species and 2 mammals (Tasmanian devil and wallaby) carry an Alanine (Ala) at t his position, raising the possibility that this change may be tolerated. Additio nal computational prediction tools suggest that the p.Asp973Ala variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Asp973Ala v ariant is uncertain, these data suggest that it is more likely to be benign. - |
Autosomal recessive nonsyndromic hearing loss 84B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 18, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at