chr2-26458102-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_194323.3(OTOF):āc.3631A>Gā(p.Met1211Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1211L) has been classified as Uncertain significance.
Frequency
Consequence
NM_194323.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194323.3 | c.3631A>G | p.Met1211Val | missense_variant | 29/29 | ENST00000339598.8 | |
OTOF | NM_194248.3 | c.*136A>G | 3_prime_UTR_variant | 47/47 | ENST00000272371.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000339598.8 | c.3631A>G | p.Met1211Val | missense_variant | 29/29 | 1 | NM_194323.3 | ||
OTOF | ENST00000272371.7 | c.*136A>G | 3_prime_UTR_variant | 47/47 | 1 | NM_194248.3 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251320Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135852
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727238
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 31, 2017 | The p.Met1211Val variant in OTOF has not been previously reported in individuals with hearing loss, but has been identified in 1/111650 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). Alth ough this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and co nservation analyses do not provide strong support for or against an impact to th e protein. In summary, the clinical significance of this variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at