rs370298976
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001378609.3(OTOGL):c.708C>T(p.Asp236=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000949 in 1,598,528 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00065 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00098 ( 17 hom. )
Consequence
OTOGL
NM_001378609.3 synonymous
NM_001378609.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.98
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 Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 12-80232988-C-T is Benign according to our data. Variant chr12-80232988-C-T is described in ClinVar as [Benign]. Clinvar id is 226974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.98 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00065 (99/152272) while in subpopulation SAS AF= 0.00975 (47/4822). AF 95% confidence interval is 0.00753. There are 0 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 17 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.708C>T | p.Asp236= | synonymous_variant | 9/59 | ENST00000547103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.708C>T | p.Asp236= | synonymous_variant | 9/59 | 5 | NM_001378609.3 | P1 | |
OTOGL | ENST00000646859.1 | c.708C>T | p.Asp236= | synonymous_variant | 14/63 | ||||
OTOGL | ENST00000643417.1 | n.1368C>T | non_coding_transcript_exon_variant | 12/23 |
Frequencies
GnomAD3 genomes AF: 0.000651 AC: 99AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00171 AC: 401AN: 234356Hom.: 7 AF XY: 0.00228 AC XY: 292AN XY: 128080
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GnomAD4 exome AF: 0.000980 AC: 1418AN: 1446256Hom.: 17 Cov.: 31 AF XY: 0.00129 AC XY: 931AN XY: 719874
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GnomAD4 genome AF: 0.000650 AC: 99AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.000658 AC XY: 49AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | OTOGL: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 04, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 05, 2016 | p.Asp227Asp in exon 8 of OTOGL: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 1% (160/16356) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at