Variant rs753923439 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_001378609.3(OTOGL):c.119+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000758 in 1,476,936 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00050 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 2 hom. )

Consequence

OTOGL
NM_001378609.3 splice_region, intron

Scores

Splicing: ADA: 0.004057

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.00

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP6

Variant 12-80210893-A-G is Benign according to our data. Variant chr12-80210893-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 227827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOGL	NM_001378609.3 linkuse as main transcript	c.119+7A>G		splice_region_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.119+7A>G	splice_region_variant, intron_variant	5	NM_001378609.3	ENSP00000447211	P1
OTOGL	ENST00000646859.1 linkuse as main transcript	c.119+7A>G	splice_region_variant, intron_variant			ENSP00000496036
OTOGL	ENST00000643417.1 linkuse as main transcript	n.779+7A>G	splice_region_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000500

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00104

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000238

AC:

AN:

113338

Hom.:

AF XY:

0.000288

AC XY:

AN XY:

62536

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000590

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000788

AC:

1044

AN:

1324798

Hom.:

Cov.:

AF XY:

0.000801

AC XY:

524

AN XY:

654182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000414

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000304

Gnomad4 NFE exome

AF:

0.000950

Gnomad4 OTH exome

AF:

0.000973

GnomAD4 genome

AF:

0.000500

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000641

Hom.:

Bravo

AF:

0.000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 27, 2015	c.92+7A>G variant in OTOGL: This variant is not expected to have clinical signif icance because it is not located within the splice consensus sequence. -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 22, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	OTOGL: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0041

dbscSNV1_RF

Benign

0.084

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.22

Position offset: -7

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