rs141972928
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_194248.3(OTOF):c.3332C>T(p.Pro1111Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P1111P) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.3332C>T | p.Pro1111Leu | missense_variant | 27/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.1091C>T | p.Pro364Leu | missense_variant | 10/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.3332C>T | p.Pro1111Leu | missense_variant | 27/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.1091C>T | p.Pro364Leu | missense_variant | 10/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000322 AC: 49AN: 152122Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000719 AC: 18AN: 250392Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135708
GnomAD4 exome AF: 0.0000472 AC: 69AN: 1460772Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 39AN XY: 726702
GnomAD4 genome ? AF: 0.000342 AC: 52AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74424
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 9 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Otorhinolaryngology Lab - LIM32, University of Sao Paulo School of Medicine Clinics Hospital | - | in compound heterozygosis with the c.2153G>A variant ina subject with bilateral non-syndromic prelingual auditory neuropathy (sporadic) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 01, 2014 | The Pro1111Leu variant in OTOF has not been previously reported in individuals w ith hearing loss, but has been identified in 0.14% (6/4406) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS/; dbSNP rs141972928). Computational prediction tools and conservation analys is suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, additional informa tion is needed to fully assess the clinical significance of this variant. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at