rs80356569
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_194248.3(OTOF):c.2317C>T(p.Arg773Cys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,602,582 control chromosomes in the GnomAD database, including 257 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R773S) has been classified as Likely benign.
Frequency
Consequence
NM_194248.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.2317C>T | p.Arg773Cys | missense_variant, splice_region_variant | 20/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.76C>T | p.Arg26Cys | missense_variant, splice_region_variant | 3/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.2317C>T | p.Arg773Cys | missense_variant, splice_region_variant | 20/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.76C>T | p.Arg26Cys | missense_variant, splice_region_variant | 3/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0156 AC: 2377AN: 152128Hom.: 30 Cov.: 32
GnomAD3 exomes AF: 0.0154 AC: 3504AN: 227648Hom.: 40 AF XY: 0.0158 AC XY: 1951AN XY: 123548
GnomAD4 exome AF: 0.0139 AC: 20232AN: 1450336Hom.: 227 Cov.: 33 AF XY: 0.0144 AC XY: 10352AN XY: 720362
GnomAD4 genome ? AF: 0.0156 AC: 2377AN: 152246Hom.: 30 Cov.: 32 AF XY: 0.0153 AC XY: 1140AN XY: 74452
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 08, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 19, 2018 | This variant is associated with the following publications: (PMID: 22607986, 12114484, 16371502, 19461658) - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 05, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 20, 2009 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Autosomal recessive nonsyndromic hearing loss 9 Benign:1Other:1
Likely benign, 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at