Variant chr12-80336781-C-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_001378609.3(OTOGL):c.4744-5dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 1,107,664 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 1 hom., cov: 26)

Exomes 𝑓: 0.021 ( 0 hom. )

Consequence

OTOGL
NM_001378609.3 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.465

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]

OTOGL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 12-80336781-C-CT is Benign according to our data. Variant chr12-80336781-C-CT is described in ClinVar as [Benign]. Clinvar id is 1987155.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0208 (19939/959764) while in subpopulation EAS AF= 0.0267 (520/19492). AF 95% confidence interval is 0.0248. There are 0 homozygotes in gnomad4_exome. There are 9680 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOGL	NM_001378609.3 linkuse as main transcript	c.4744-5dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
OTOGL	ENST00000547103.7 linkuse as main transcript	c.4744-5dup	splice_polypyrimidine_tract_variant, intron_variant	5	NM_001378609.3	ENSP00000447211	P1
OTOGL	ENST00000298820.7 linkuse as main transcript	c.45-5dup	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000298820
OTOGL	ENST00000646859.1 linkuse as main transcript	c.4609-5dup	splice_polypyrimidine_tract_variant, intron_variant			ENSP00000496036

Frequencies

GnomAD3 genomes

AF:

0.000298

AC:

AN:

147824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000272

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000404

Gnomad ASJ

AF:

0.000294

Gnomad EAS

AF:

0.000791

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00115

Gnomad MID

AF:

0.00993

Gnomad NFE

AF:

0.000120

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0208

AC:

19939

AN:

959764

Hom.:

Cov.:

AF XY:

0.0204

AC XY:

9680

AN XY:

473672

show subpopulations

Gnomad4 AFR exome

AF:

0.0206

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.0228

Gnomad4 EAS exome

AF:

0.0267

Gnomad4 SAS exome

AF:

0.0222

Gnomad4 FIN exome

AF:

0.0189

Gnomad4 NFE exome

AF:

0.0204

Gnomad4 OTH exome

AF:

0.0224

GnomAD4 genome

AF:

0.000304

AC:

AN:

147900

Hom.:

Cov.:

AF XY:

0.000361

AC XY:

AN XY:

72046

show subpopulations

Gnomad4 AFR

AF:

0.000296

Gnomad4 AMR

AF:

0.000404

Gnomad4 ASJ

AF:

0.000294

Gnomad4 EAS

AF:

0.000793

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00115

Gnomad4 NFE

AF:

0.000120

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over