rs575344158

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_001292063.2(OTOG):​c.1050C>T​(p.His350=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,550,464 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00051 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00051 ( 1 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.370
Variant links:
Genes affected
OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 11-17558591-C-T is Benign according to our data. Variant chr11-17558591-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 514533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.37 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OTOGNM_001292063.2 linkuse as main transcriptc.1050C>T p.His350= synonymous_variant 10/56 ENST00000399397.6 NP_001278992.1
OTOGNM_001277269.2 linkuse as main transcriptc.1086C>T p.His362= synonymous_variant 9/55 NP_001264198.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OTOGENST00000399397.6 linkuse as main transcriptc.1050C>T p.His350= synonymous_variant 10/565 NM_001292063.2 ENSP00000382329 P2
OTOGENST00000399391.7 linkuse as main transcriptc.1086C>T p.His362= synonymous_variant 9/555 ENSP00000382323 A2Q6ZRI0-1
OTOGENST00000485669.1 linkuse as main transcriptn.534C>T non_coding_transcript_exon_variant 3/34
OTOGENST00000498332.5 linkuse as main transcriptn.956C>T non_coding_transcript_exon_variant 9/165

Frequencies

GnomAD3 genomes
AF:
0.000519
AC:
79
AN:
152232
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00461
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00217
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000500
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000850
AC:
125
AN:
147066
Hom.:
0
AF XY:
0.000958
AC XY:
76
AN XY:
79340
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000285
Gnomad ASJ exome
AF:
0.00454
Gnomad EAS exome
AF:
0.0000927
Gnomad SAS exome
AF:
0.000799
Gnomad FIN exome
AF:
0.00215
Gnomad NFE exome
AF:
0.000478
Gnomad OTH exome
AF:
0.000469
GnomAD4 exome
AF:
0.000514
AC:
719
AN:
1398114
Hom.:
1
Cov.:
33
AF XY:
0.000500
AC XY:
345
AN XY:
689588
show subpopulations
Gnomad4 AFR exome
AF:
0.0000316
Gnomad4 AMR exome
AF:
0.000280
Gnomad4 ASJ exome
AF:
0.00492
Gnomad4 EAS exome
AF:
0.000112
Gnomad4 SAS exome
AF:
0.000682
Gnomad4 FIN exome
AF:
0.00202
Gnomad4 NFE exome
AF:
0.000359
Gnomad4 OTH exome
AF:
0.000707
GnomAD4 genome
AF:
0.000512
AC:
78
AN:
152350
Hom.:
1
Cov.:
33
AF XY:
0.000550
AC XY:
41
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00461
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00217
Gnomad4 NFE
AF:
0.000500
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000793
Hom.:
0
Bravo
AF:
0.000310
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign/Likely 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 02, 2022- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2022OTOG: BP4, BP7 -
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 05, 2020- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineAug 10, 2017p.His362His in exon 9 of OTOG: 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 also been identified in 0.4% (35/8398) of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, htt p://gnomad.broadinstitute.org; dbSNP rs575344158). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
3.4
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs575344158; hg19: chr11-17580138; API