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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378609.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOGL	NM_001378609.3	MANE Select	c.2391-6G>A		splice_region intron	N/A	NP_001365538.2	Q3ZCN5
	OTOGL	NM_001378610.3		c.2391-6G>A		splice_region intron	N/A	NP_001365539.2	Q3ZCN5
	OTOGL	NM_173591.7		c.2391-6G>A		splice_region intron	N/A	NP_775862.4	Q3ZCN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOGL	ENST00000547103.7	TSL:5 MANE Select	c.2391-6G>A		splice_region intron	N/A	ENSP00000447211.2	Q3ZCN5
	OTOGL	ENST00000646859.1		c.2391-6G>A		splice_region intron	N/A	ENSP00000496036.1	A0A2R8YF04

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

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;