chr12-80210860-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_001378609.3(OTOGL):ā€‹c.93A>Gā€‹(p.Ala31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,477,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0014 ( 0 hom., cov: 32)
Exomes š‘“: 0.00012 ( 0 hom. )

Consequence

OTOGL
NM_001378609.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.416
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 12-80210860-A-G is Benign according to our data. Variant chr12-80210860-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 504789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80210860-A-G is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.416 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0014 (213/152228) while in subpopulation AFR AF= 0.005 (208/41562). AF 95% confidence interval is 0.00445. There are 0 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OTOGLNM_001378609.3 linkuse as main transcriptc.93A>G p.Ala31= synonymous_variant 3/59 ENST00000547103.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OTOGLENST00000547103.7 linkuse as main transcriptc.93A>G p.Ala31= synonymous_variant 3/595 NM_001378609.3 P1
OTOGLENST00000646859.1 linkuse as main transcriptc.93A>G p.Ala31= synonymous_variant 8/63
OTOGLENST00000643417.1 linkuse as main transcriptn.753A>G non_coding_transcript_exon_variant 6/23

Frequencies

GnomAD3 genomes
AF:
0.00139
AC:
212
AN:
152110
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00500
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
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:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000126
AC:
14
AN:
111244
Hom.:
0
AF XY:
0.0000653
AC XY:
4
AN XY:
61250
show subpopulations
Gnomad AFR exome
AF:
0.00273
Gnomad AMR exome
AF:
0.000106
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000121
AC:
160
AN:
1325060
Hom.:
0
Cov.:
28
AF XY:
0.000101
AC XY:
66
AN XY:
654250
show subpopulations
Gnomad4 AFR exome
AF:
0.00482
Gnomad4 AMR exome
AF:
0.000257
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:
9.60e-7
Gnomad4 OTH exome
AF:
0.000198
GnomAD4 genome
AF:
0.00140
AC:
213
AN:
152228
Hom.:
0
Cov.:
32
AF XY:
0.00137
AC XY:
102
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00500
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000856
Hom.:
0
Bravo
AF:
0.00143
Asia WGS
AF:
0.000578
AC:
2
AN:
3476

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 03, 2023- -
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 10, 2021- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineJul 20, 2017p.Ala22Ala in exon 2 of OTOGL: 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 been identified in 0.4% (49/12956) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.br oadinstitute.org; dbSNP rs147902353). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
1.2
DANN
Benign
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs147902353; hg19: chr12-80604640; API