chr12-80210860-A-G
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_001378609.3(OTOGL):āc.93A>Gā(p.Ala31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,477,288 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.0014 ( 0 hom., cov: 32)
Exomes š: 0.00012 ( 0 hom. )
Consequence
OTOGL
NM_001378609.3 synonymous
NM_001378609.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.416
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 -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 12-80210860-A-G is Benign according to our data. Variant chr12-80210860-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 504789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80210860-A-G is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.416 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0014 (213/152228) while in subpopulation AFR AF= 0.005 (208/41562). AF 95% confidence interval is 0.00445. There are 0 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.93A>G | p.Ala31= | synonymous_variant | 3/59 | ENST00000547103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.93A>G | p.Ala31= | synonymous_variant | 3/59 | 5 | NM_001378609.3 | P1 | |
OTOGL | ENST00000646859.1 | c.93A>G | p.Ala31= | synonymous_variant | 8/63 | ||||
OTOGL | ENST00000643417.1 | n.753A>G | non_coding_transcript_exon_variant | 6/23 |
Frequencies
GnomAD3 genomes AF: 0.00139 AC: 212AN: 152110Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000126 AC: 14AN: 111244Hom.: 0 AF XY: 0.0000653 AC XY: 4AN XY: 61250
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GnomAD4 exome AF: 0.000121 AC: 160AN: 1325060Hom.: 0 Cov.: 28 AF XY: 0.000101 AC XY: 66AN XY: 654250
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GnomAD4 genome AF: 0.00140 AC: 213AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.00137 AC XY: 102AN XY: 74436
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 03, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 20, 2017 | p.Ala22Ala in exon 2 of OTOGL: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.4% (49/12956) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.br oadinstitute.org; dbSNP rs147902353). - |
Computational scores
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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