rs149236286
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_194248.3(OTOF):c.4332C>T(p.Thr1444Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,613,904 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_194248.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.4332C>T | p.Thr1444Thr | synonymous_variant | Exon 35 of 47 | 1 | NM_194248.3 | ENSP00000272371.2 | ||
OTOF | ENST00000339598.8 | c.2031C>T | p.Thr677Thr | synonymous_variant | Exon 18 of 29 | 1 | NM_194323.3 | ENSP00000344521.3 |
Frequencies
GnomAD3 genomes AF: 0.0146 AC: 2219AN: 152088Hom.: 18 Cov.: 32
GnomAD3 exomes AF: 0.0144 AC: 3622AN: 251204Hom.: 29 AF XY: 0.0146 AC XY: 1988AN XY: 135808
GnomAD4 exome AF: 0.0195 AC: 28459AN: 1461698Hom.: 353 Cov.: 35 AF XY: 0.0189 AC XY: 13757AN XY: 727170
GnomAD4 genome AF: 0.0146 AC: 2221AN: 152206Hom.: 18 Cov.: 32 AF XY: 0.0136 AC XY: 1014AN XY: 74398
ClinVar
Submissions by phenotype
not provided Benign:4
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This variant is associated with the following publications: (PMID: 19461658, 18381613) -
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Autosomal recessive nonsyndromic hearing loss 9 Uncertain:1
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
Thr1444Thr in exon 35 of OTOF: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located near a splice junction, is reported as benign in one publication (Rodriguez-Ballestero s 2008) and has been identified in 5/211 (2.4%) probands tested by our laborator y (at least 2 have Usher syndrome). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at