rs200191563
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_194248.3(OTOF):c.1640C>T(p.Thr547Met) variant causes a missense change. The variant allele was found at a frequency of 0.000307 in 1,613,046 control chromosomes in the GnomAD database, including 1 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. T547T) has been classified as Likely benign.
Frequency
Consequence
NM_194248.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.1640C>T | p.Thr547Met | missense_variant | 15/47 | ENST00000272371.7 | |
OTOF | NM_001287489.2 | c.1640C>T | p.Thr547Met | missense_variant | 15/46 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.1640C>T | p.Thr547Met | missense_variant | 15/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000403946.7 | c.1640C>T | p.Thr547Met | missense_variant | 15/46 | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000374 AC: 57AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000593 AC: 148AN: 249768Hom.: 0 AF XY: 0.000531 AC XY: 72AN XY: 135568
GnomAD4 exome AF: 0.000301 AC: 439AN: 1460722Hom.: 1 Cov.: 33 AF XY: 0.000279 AC XY: 203AN XY: 726642
GnomAD4 genome ? AF: 0.000374 AC: 57AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.000389 AC XY: 29AN XY: 74488
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 16, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | The c.1640C>T (p.T547M) alteration is located in exon 15 (coding exon 15) of the OTOF gene. This alteration results from a C to T substitution at nucleotide position 1640, causing the threonine (T) at amino acid position 547 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal recessive nonsyndromic hearing loss 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 26, 2017 | p.Thr547Met in exon 15 of OTOF: This variant is not expected to have clinical si gnificance because it has been identified in 0.3% (95/34410) of Latino chromosom es by Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbS NP rs200191563). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at