rs141235641
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_194248.3(OTOF):c.5742G>A(p.Leu1914=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,614,062 control chromosomes in the GnomAD database, including 5 homozygotes. 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. L1914L) has been classified as Likely benign.
Frequency
Consequence
NM_194248.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.5742G>A | p.Leu1914= | synonymous_variant | 45/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.3441G>A | p.Leu1147= | synonymous_variant | 28/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.5742G>A | p.Leu1914= | synonymous_variant | 45/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.3441G>A | p.Leu1147= | synonymous_variant | 28/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00184 AC: 280AN: 152100Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00173 AC: 435AN: 251172Hom.: 0 AF XY: 0.00165 AC XY: 224AN XY: 135766
GnomAD4 exome AF: 0.00183 AC: 2671AN: 1461844Hom.: 3 Cov.: 35 AF XY: 0.00186 AC XY: 1353AN XY: 727224
GnomAD4 genome ? AF: 0.00184 AC: 280AN: 152218Hom.: 2 Cov.: 32 AF XY: 0.00180 AC XY: 134AN XY: 74430
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:4
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | OTOF: BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 12, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 05, 2019 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 05, 2017 | p.Leu1914Leu in exon 45 of OTOF: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.3% (409/126530) o f European chromosomes including 2 homozygotes by the genome Aggregation Databas e (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs141235641). - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 14, 2023 | - - |
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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at