11-17553506-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001292063.2(OTOG):​c.527G>T​(p.Ser176Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OTOG
NM_001292063.2 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2855118).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OTOGNM_001292063.2 linkc.527G>T p.Ser176Ile missense_variant Exon 6 of 56 ENST00000399397.6 NP_001278992.1 H9KVB3
OTOGNM_001277269.2 linkc.563G>T p.Ser188Ile missense_variant Exon 5 of 55 NP_001264198.1 Q6ZRI0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OTOGENST00000399397.6 linkc.527G>T p.Ser176Ile missense_variant Exon 6 of 56 5 NM_001292063.2 ENSP00000382329.2 H9KVB3
OTOGENST00000399391.7 linkc.563G>T p.Ser188Ile missense_variant Exon 5 of 55 5 ENSP00000382323.2 Q6ZRI0-1
OTOGENST00000498332.5 linkn.433G>T non_coding_transcript_exon_variant Exon 5 of 16 5
OTOGENST00000428619.1 linkc.*62G>T downstream_gene_variant 3 ENSP00000399057.2 C9IZ84

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1289924
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
624430
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.21
T;.
Eigen
Benign
0.11
Eigen_PC
Benign
0.071
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Benign
-0.51
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-2.2
N;.
REVEL
Uncertain
0.36
Sift
Benign
0.056
T;.
Sift4G
Uncertain
0.0020
D;D
Vest4
0.12
MutPred
0.67
Loss of disorder (P = 0.005);.;
MVP
0.52
ClinPred
0.23
T
GERP RS
2.3
Varity_R
0.099
gMVP
0.42

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: rs876657556; hg19: chr11-17575053; API