rs77835094
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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.2550C>T(p.Phe850=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000998 in 1,612,896 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00097 ( 14 hom. )
Consequence
OTOGL
NM_001378609.3 synonymous
NM_001378609.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.317
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=-0.33).
BP6
?
Variant 12-80271679-C-T is Benign according to our data. Variant chr12-80271679-C-T is described in ClinVar as [Benign]. Clinvar id is 226933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80271679-C-T is described in Lovd as [Benign]. Variant chr12-80271679-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.317 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00122 (186/152118) while in subpopulation EAS AF= 0.0175 (90/5152). AF 95% confidence interval is 0.0146. There are 1 homozygotes in gnomad4. There are 103 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.2550C>T | p.Phe850= | synonymous_variant | 24/59 | ENST00000547103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.2550C>T | p.Phe850= | synonymous_variant | 24/59 | 5 | NM_001378609.3 | P1 | |
OTOGL | ENST00000646859.1 | c.2550C>T | p.Phe850= | synonymous_variant | 29/63 |
Frequencies
GnomAD3 genomes ? AF: 0.00122 AC: 186AN: 152000Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00257 AC: 631AN: 245792Hom.: 6 AF XY: 0.00234 AC XY: 313AN XY: 133546
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GnomAD4 exome AF: 0.000974 AC: 1423AN: 1460778Hom.: 14 Cov.: 32 AF XY: 0.000928 AC XY: 674AN XY: 726676
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GnomAD4 genome ? AF: 0.00122 AC: 186AN: 152118Hom.: 1 Cov.: 32 AF XY: 0.00139 AC XY: 103AN XY: 74348
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ClinVar
Significance: 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 | Invitae | Nov 21, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 23, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Phe841Phe in exon 23 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 1.9% (11/572) of Ea st Asian chromosomes from a broad population by the 1000 Genomes Project (http:/ /www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs77835094). - |
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