2-26475949-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_194248.3(OTOF):c.2956C>T(p.Arg986Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,611,546 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R986R) has been classified as Likely benign.
Frequency
Consequence
NM_194248.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.2956C>T | p.Arg986Cys | missense_variant | 24/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.715C>T | p.Arg239Cys | missense_variant | 7/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.2956C>T | p.Arg986Cys | missense_variant | 24/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.715C>T | p.Arg239Cys | missense_variant | 7/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000811 AC: 20AN: 246528Hom.: 0 AF XY: 0.0000822 AC XY: 11AN XY: 133830
GnomAD4 exome AF: 0.000112 AC: 163AN: 1459330Hom.: 0 Cov.: 33 AF XY: 0.000105 AC XY: 76AN XY: 725824
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74424
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 | Mar 15, 2016 | The p.Arg986Cys variant in OTOF has not been previously reported in individuals with hearing loss, but has been identified in 9/50616 European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs20 1198797). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg986Cys variant is uncertain. - |
Autosomal recessive nonsyndromic hearing loss 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 04, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 15, 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