rs11893228
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_194248.3(OTOF):c.5039G>A(p.Arg1680His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 1,613,702 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. R1680C) has been classified as Uncertain significance.
Frequency
Consequence
NM_194248.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.5039G>A | p.Arg1680His | missense_variant | 40/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.2738G>A | p.Arg913His | missense_variant | 23/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.5039G>A | p.Arg1680His | missense_variant | 40/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.2738G>A | p.Arg913His | missense_variant | 23/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00312 AC: 475AN: 152194Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.000854 AC: 214AN: 250618Hom.: 1 AF XY: 0.000605 AC XY: 82AN XY: 135644
GnomAD4 exome AF: 0.000307 AC: 448AN: 1461390Hom.: 4 Cov.: 32 AF XY: 0.000241 AC XY: 175AN XY: 727004
GnomAD4 genome ? AF: 0.00311 AC: 474AN: 152312Hom.: 5 Cov.: 32 AF XY: 0.00294 AC XY: 219AN XY: 74476
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | OTOF: BP4, BS1, BS2 - |
Autosomal recessive nonsyndromic hearing loss 9 Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Arg1680His in Exon 40 of OTOF: This variant is not expected to have clinical sig nificance because it has been identified in 0.7% (25/3738) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs11893228). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at