rs112430701
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001378609.3(OTOGL):c.2551G>A(p.Asp851Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00018 in 1,612,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
OTOGL
NM_001378609.3 missense
NM_001378609.3 missense
Scores
2
10
Clinical Significance
Conservation
PhyloP100: 4.77
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.014784217).
BP6
?
Variant 12-80271680-G-A is Benign according to our data. Variant chr12-80271680-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 227817.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.2551G>A | p.Asp851Asn | missense_variant | 24/59 | ENST00000547103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.2551G>A | p.Asp851Asn | missense_variant | 24/59 | 5 | NM_001378609.3 | P1 | |
OTOGL | ENST00000646859.1 | c.2551G>A | p.Asp851Asn | missense_variant | 29/63 |
Frequencies
GnomAD3 genomes ? AF: 0.000639 AC: 97AN: 151918Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
97
AN:
151918
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000146 AC: 36AN: 245858Hom.: 0 AF XY: 0.0000823 AC XY: 11AN XY: 133598
GnomAD3 exomes
AF:
AC:
36
AN:
245858
Hom.:
AF XY:
AC XY:
11
AN XY:
133598
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000132 AC: 193AN: 1460776Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 88AN XY: 726676
GnomAD4 exome
AF:
AC:
193
AN:
1460776
Hom.:
Cov.:
32
AF XY:
AC XY:
88
AN XY:
726676
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000638 AC: 97AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.000592 AC XY: 44AN XY: 74298
GnomAD4 genome
?
AF:
AC:
97
AN:
152036
Hom.:
Cov.:
32
AF XY:
AC XY:
44
AN XY:
74298
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
7
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
24
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 25, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 22, 2015 | p.Asp842Asn in exon 23 of OTOGL: This variant is not expected to have clinical s ignificance because it has been identified in 0.2% (20/9728) of African chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs112430701) and due to a lack of conservation across species, including ma mmals. Of note, bat, microbat, and big brown bat have an asparagine (Asn) at thi s position despite high nearby amino acid conservation. In addition, computation al prediction tools suggest that the p.Asp842Asn variant may not impact the prot ein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Vest4
0.30
MVP
0.27
MPC
0.033
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at