11-17547466-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001292063.2(OTOG):​c.94G>T​(p.Ala32Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000246 in 1,217,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

OTOG
NM_001292063.2 missense, splice_region

Scores

2
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OTOGNM_001292063.2 linkc.94G>T p.Ala32Ser missense_variant, splice_region_variant Exon 1 of 56 ENST00000399397.6 NP_001278992.1 H9KVB3
OTOGNM_001277269.2 linkc.94G>T p.Gly32Cys missense_variant Exon 1 of 55 NP_001264198.1 Q6ZRI0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OTOGENST00000399397.6 linkc.94G>T p.Ala32Ser missense_variant, splice_region_variant Exon 1 of 56 5 NM_001292063.2 ENSP00000382329.2 H9KVB3
OTOGENST00000399391.7 linkc.94G>T p.Gly32Cys missense_variant Exon 1 of 55 5 ENSP00000382323.2 Q6ZRI0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000246
AC:
3
AN:
1217442
Hom.:
0
Cov.:
31
AF XY:
0.00000338
AC XY:
2
AN XY:
591432
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000684
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000193
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000100
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
22
DANN
Uncertain
0.99
Eigen
Benign
-0.099
Eigen_PC
Benign
-0.10
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.16
T
Sift4G
Benign
0.34
T
Vest4
0.22
MVP
0.072
ClinPred
0.76
D
GERP RS
3.3

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.62
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.25
Position offset: -39
DS_DL_spliceai
0.62
Position offset: 0

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: rs565203765; hg19: chr11-17569013; API