rs9783425

Variant names:

• chr12-80267247-G-A
• rs9783425
• NM_001378609.3:c.2391-6G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-80267247-G-A
• chr12-80267247-G-C
• chr12-80267247-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378609.3(OTOGL):​c.2391-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,513,180 control chromosomes in the GnomAD database, including 1,321 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (720 hom., cov: 31)
  • Exomes 𝑓: 0.0054 (601 hom.)
• Consequence: OTOGL NM_001378609.3 splice_region, intron
• Scores: Splicing: ADA: 0.00004326
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.66
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 84B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-80267247-G-A is Benign according to our data. Variant chr12-80267247-G-A is described in ClinVar as Benign. ClinVar VariationId is 226932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.2391-6G>A		splice_region_variant, intron_variant	Intron 21 of 58	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.2391-6G>A		splice_region_variant, intron_variant	Intron 21 of 58	5	NM_001378609.3	ENSP00000447211.2
OTOGL	ENST00000646859.1	c.2391-6G>A		splice_region_variant, intron_variant	Intron 26 of 62			ENSP00000496036.1

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8217 AN: 151596 Hom.: 716 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.000573

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.0378

GnomAD2 exomes AF: 0.0123 AC: 2279 AN: 185720 AF XY: 0.00934

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.00833

Gnomad ASJ exome AF: 0.000113

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000616

Gnomad OTH exome AF: 0.00632

GnomAD4 exome AF: 0.00543 AC: 7389 AN: 1361472 Hom.: 601 Cov.: 28 AF XY: 0.00467 AC XY: 3157 AN XY: 676106

African (AFR) AF: 0.193 AC: 5892 AN: 30606

American (AMR) AF: 0.00983 AC: 374 AN: 38054

Ashkenazi Jewish (ASJ) AF: 0.0000406 AC: 1 AN: 24602

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37136

South Asian (SAS) AF: 0.000450 AC: 35 AN: 77820

European-Finnish (FIN) AF: 0.000237 AC: 12 AN: 50692

Middle Eastern (MID) AF: 0.00773 AC: 43 AN: 5566

European-Non Finnish (NFE) AF: 0.000327 AC: 340 AN: 1040352

Other (OTH) AF: 0.0122 AC: 691 AN: 56644

GnomAD4 genome AF: 0.0543 AC: 8235 AN: 151708 Hom.: 720 Cov.: 31 AF XY: 0.0516 AC XY: 3824 AN XY: 74112

African (AFR) AF: 0.190 AC: 7843 AN: 41338

American (AMR) AF: 0.0166 AC: 253 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4808

European-Finnish (FIN) AF: 0.000573 AC: 6 AN: 10466

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000663 AC: 45 AN: 67922

Other (OTH) AF: 0.0374 AC: 79 AN: 2110

Alfa AF: 0.0210 Hom.: 159

Bravo AF: 0.0628

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 23, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Nov 17, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

2364-6G>A in intron 20 of OTOGL: This variant is not expected to have clinical s ignificance because it has been identified in 18.5% (678/3662) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs9783425). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.42
PhyloP100		1.7
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000043
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs9783425; hg19: chr12-80661027;