rs369730291
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001378609.3(OTOGL):c.2877T>C(p.Phe959=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000696 in 1,594,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000066 ( 0 hom. )
Consequence
OTOGL
NM_001378609.3 synonymous
NM_001378609.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.10
Genes affected
OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 12-80279115-T-C is Benign according to our data. Variant chr12-80279115-T-C is described in ClinVar as [Benign]. Clinvar id is 226935.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=2.1 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.2877T>C | p.Phe959= | synonymous_variant | 26/59 | ENST00000547103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.2877T>C | p.Phe959= | synonymous_variant | 26/59 | 5 | NM_001378609.3 | P1 | |
OTOGL | ENST00000646859.1 | c.2877T>C | p.Phe959= | synonymous_variant | 31/63 |
Frequencies
GnomAD3 genomes ? AF: 0.000106 AC: 16AN: 151488Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000312 AC: 73AN: 233606Hom.: 0 AF XY: 0.000290 AC XY: 37AN XY: 127734
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GnomAD4 exome AF: 0.0000658 AC: 95AN: 1443356Hom.: 0 Cov.: 33 AF XY: 0.0000612 AC XY: 44AN XY: 718470
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GnomAD4 genome ? AF: 0.000106 AC: 16AN: 151606Hom.: 0 Cov.: 32 AF XY: 0.0000810 AC XY: 6AN XY: 74116
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 12, 2016 | p.Phe950Phe in exon 25 of OTOGL: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.4% (35/8320) o f East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs369730291). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at