rs140454738
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_194248.3(OTOF):c.446C>T(p.Thr149Met) variant causes a missense change. The variant allele was found at a frequency of 0.000211 in 1,613,742 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. T149T) has been classified as Likely benign.
Frequency
Consequence
NM_194248.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.446C>T | p.Thr149Met | missense_variant | 5/47 | ENST00000272371.7 | |
OTOF | NM_001287489.2 | c.446C>T | p.Thr149Met | missense_variant | 5/46 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.446C>T | p.Thr149Met | missense_variant | 5/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000403946.7 | c.446C>T | p.Thr149Met | missense_variant | 5/46 | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000291 AC: 73AN: 251278Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135840
GnomAD4 exome AF: 0.000218 AC: 318AN: 1461618Hom.: 0 Cov.: 33 AF XY: 0.000217 AC XY: 158AN XY: 727136
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74298
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 09, 2014 | - - |
Autosomal recessive nonsyndromic hearing loss 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 25, 2018 | p.Thr149Met in exon 5A of OTOF: This variant is not expected to have clinical si gnificance because it has also been identified in 0.34% (35/10152) of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.bro adinstitute.org/; dbSNP rs140454738). It has also been identified in 1 individua l with Usher syndrome who was found to have an alternate genetic etiology for Us her syndrome. ACMG/AMP criteria applied: BS1; BP5; PP3. - |
OTOF-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 21, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at