chr2-26464004-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP3BP4_StrongBP6
The NM_194248.3(OTOF):c.5063C>T(p.Thr1688Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,613,764 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1688K) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.5063C>T | p.Thr1688Met | missense_variant | 40/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.2762C>T | p.Thr921Met | missense_variant | 23/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.5063C>T | p.Thr1688Met | missense_variant | 40/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.2762C>T | p.Thr921Met | missense_variant | 23/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes AF: 0.00133 AC: 203AN: 152172Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00126 AC: 315AN: 250620Hom.: 0 AF XY: 0.00133 AC XY: 180AN XY: 135614
GnomAD4 exome AF: 0.00143 AC: 2095AN: 1461474Hom.: 0 Cov.: 32 AF XY: 0.00138 AC XY: 1004AN XY: 727044
GnomAD4 genome AF: 0.00133 AC: 203AN: 152290Hom.: 0 Cov.: 33 AF XY: 0.00117 AC XY: 87AN XY: 74448
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 22, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously reported in association with hearing loss to our knowledge; This variant is associated with the following publications: (PMID: 19461658) - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 04, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Autosomal recessive nonsyndromic hearing loss 9 Uncertain:1Benign: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. - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 08, 2012 | Thr1688Met in exon 40 of OTOF: This variant has been identified in three individ uals by our laboratory, none of whom had second OTOF variants and one of whom ha d another cause of hearing loss. In addition, this variant has been identified i n 0.19% (16/8600) of European American chromosomes in a broad population by the NHLBI Exome sequencing project (http://evs.gs.washington.edu/EVS/; dbSNP rs11103 3393). In summary, these data suggest this variant is likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 26, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at