rs61740776
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_194248.3(OTOF):āc.3608A>Gā(p.Asn1203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,613,348 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_194248.3 missense
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.3608A>G | p.Asn1203Ser | missense_variant | 29/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.1367A>G | p.Asn456Ser | missense_variant | 12/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.3608A>G | p.Asn1203Ser | missense_variant | 29/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.1367A>G | p.Asn456Ser | missense_variant | 12/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0156 AC: 2374AN: 152042Hom.: 53 Cov.: 33
GnomAD3 exomes AF: 0.00391 AC: 979AN: 250338Hom.: 13 AF XY: 0.00293 AC XY: 397AN XY: 135660
GnomAD4 exome AF: 0.00156 AC: 2285AN: 1461188Hom.: 51 Cov.: 33 AF XY: 0.00134 AC XY: 976AN XY: 726892
GnomAD4 genome ? AF: 0.0156 AC: 2380AN: 152160Hom.: 54 Cov.: 33 AF XY: 0.0149 AC XY: 1107AN XY: 74382
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 12, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 26, 2011 | Asn1203Ser in exon 29 of OTOF: This variant is not expected to have clinical sig nificance due to a frequency of 5.9% (7/118) in Black controls (rs61740776). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 14, 2018 | - - |
Autosomal recessive nonsyndromic hearing loss 9 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 08, 2021 | - - |
OTOF-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 13, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Bilateral sensorineural hearing impairment Benign:1
Benign, criteria provided, single submitter | research | Laboratory of Human Genetics, Institute of Biosciences - University of Sao Paulo | - | clinical significance unknown since this variant was found in single heterozygosis and a likely pathogenic heterozygous variant in FGFR2 was detected, which is more probably related to the phenotype - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at