NM_001292063.2:c.3289-8C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001292063.2(OTOG):​c.3289-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000955 in 1,550,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

OTOG
NM_001292063.2 splice_region, intron

Scores

2
Splicing: ADA: 0.00005100
2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.199

Publications

0 publications found
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]
OTOG Gene-Disease associations (from GenCC):
  • autosomal recessive nonsyndromic hearing loss 18B
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Ambry Genetics
  • nonsyndromic genetic hearing loss
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 11-17594039-C-T is Benign according to our data. Variant chr11-17594039-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1188782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OTOGNM_001292063.2 linkc.3289-8C>T splice_region_variant, intron_variant Intron 27 of 55 ENST00000399397.6 NP_001278992.1 H9KVB3
OTOGNM_001277269.2 linkc.3325-8C>T splice_region_variant, intron_variant Intron 26 of 54 NP_001264198.1 Q6ZRI0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OTOGENST00000399397.6 linkc.3289-8C>T splice_region_variant, intron_variant Intron 27 of 55 5 NM_001292063.2 ENSP00000382329.2 H9KVB3
OTOGENST00000399391.7 linkc.3325-8C>T splice_region_variant, intron_variant Intron 26 of 54 5 ENSP00000382323.2 Q6ZRI0-1
OTOGENST00000342528.2 linkn.654-8C>T splice_region_variant, intron_variant Intron 4 of 21 2

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000737
AC:
11
AN:
149176
AF XY:
0.0000373
show subpopulations
Gnomad AFR exome
AF:
0.000148
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000182
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000980
AC:
137
AN:
1398266
Hom.:
0
Cov.:
32
AF XY:
0.000103
AC XY:
71
AN XY:
689650
show subpopulations
African (AFR)
AF:
0.0000633
AC:
2
AN:
31598
American (AMR)
AF:
0.00
AC:
0
AN:
35700
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25182
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35738
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79226
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48166
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5696
European-Non Finnish (NFE)
AF:
0.000123
AC:
133
AN:
1078966
Other (OTH)
AF:
0.0000345
AC:
2
AN:
57994
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
8
16
24
32
40
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74376
show subpopulations
African (AFR)
AF:
0.0000482
AC:
2
AN:
41460
American (AMR)
AF:
0.00
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000132
AC:
9
AN:
68038
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000727
Hom.:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jan 07, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Oct 29, 2020
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
1.1
DANN
Benign
0.32
PhyloP100
-0.20
Mutation Taster
=97/3
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000051
dbscSNV1_RF
Benign
0.0
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

Other links and lift over

dbSNP: rs12792504; hg19: chr11-17615586; API