rs76420383
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001378609.3(OTOGL):c.1990C>T(p.Pro664Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,610,908 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0019 ( 17 hom. )
Consequence
OTOGL
NM_001378609.3 missense
NM_001378609.3 missense
Scores
2
4
5
Clinical Significance
Conservation
PhyloP100: 7.42
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.011739701).
BP6
?
Variant 12-80262069-C-T is Benign according to our data. Variant chr12-80262069-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 226931.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=3, Uncertain_significance=1}. Variant chr12-80262069-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00159 (242/152142) while in subpopulation SAS AF= 0.00686 (33/4814). AF 95% confidence interval is 0.00502. There are 0 homozygotes in gnomad4. There are 116 alleles in male gnomad4 subpopulation. Median coverage is 33. 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.1990C>T | p.Pro664Ser | missense_variant | 19/59 | ENST00000547103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.1990C>T | p.Pro664Ser | missense_variant | 19/59 | 5 | NM_001378609.3 | P1 | |
OTOGL | ENST00000646859.1 | c.1990C>T | p.Pro664Ser | missense_variant | 24/63 | ||||
OTOGL | ENST00000643417.1 | n.2650C>T | non_coding_transcript_exon_variant | 22/23 |
Frequencies
GnomAD3 genomes ? AF: 0.00161 AC: 245AN: 152024Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00248 AC: 609AN: 245976Hom.: 4 AF XY: 0.00295 AC XY: 394AN XY: 133684
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GnomAD4 exome AF: 0.00193 AC: 2810AN: 1458766Hom.: 17 Cov.: 31 AF XY: 0.00228 AC XY: 1657AN XY: 725640
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GnomAD4 genome ? AF: 0.00159 AC: 242AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.00156 AC XY: 116AN XY: 74374
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ExAC
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Asia WGS
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | OTOGL: BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2019 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Aug 24, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 16, 2015 | p.Pro655Ser in exon 18 of OTOGL: This variant is not expected to have clinical s ignificance because it has been identified in 0.9% (149/16498) of South Asian ch romosomes including 2 homozygotes by the Exome Aggregation Consortium (ExAC, htt p://exac.broadinstitute.org; dbSNP rs76420383). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2021 | The c.1963C>T (p.P655S) alteration is located in exon 18 (coding exon 18) of the OTOGL gene. This alteration results from a C to T substitution at nucleotide position 1963, causing the proline (P) at amino acid position 655 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Vest4
0.80
MVP
0.29
MPC
0.19
ClinPred
T
GERP RS
gMVP
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