rs78377084

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001378609.3(OTOGL):c.1111C>T(p.His371Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,593,514 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. H371H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

OTOGL
NM_001378609.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 7.57

Publications

4 publications found

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 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

OTOGL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01437515).

BP6

Variant 12-80251751-C-T is Benign according to our data. Variant chr12-80251751-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 227810.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000177 (27/152242) while in subpopulation EAS AF = 0.00522 (27/5170). AF 95% confidence interval is 0.00369. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTOGL	NM_001378609.3	MANE Select	c.1111C>T	p.His371Tyr	missense	Exon 12 of 59	NP_001365538.2	Q3ZCN5
OTOGL	NM_001378610.3		c.1111C>T	p.His371Tyr	missense	Exon 15 of 62	NP_001365539.2	Q3ZCN5
OTOGL	NM_173591.7		c.1111C>T	p.His371Tyr	missense	Exon 12 of 59	NP_775862.4	Q3ZCN5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTOGL	ENST00000547103.7	TSL:5 MANE Select	c.1111C>T	p.His371Tyr	missense	Exon 12 of 59	ENSP00000447211.2	Q3ZCN5
OTOGL	ENST00000646859.1		c.1111C>T	p.His371Tyr	missense	Exon 17 of 63	ENSP00000496036.1	A0A2R8YF04
OTOGL	ENST00000643417.1		n.1771C>T		non_coding_transcript_exon	Exon 15 of 23

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00521

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000372

AC:

AN:

214874

AF XY:

0.000417

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00489

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000184

GnomAD4 exome

AF:

0.0000923

AC:

133

AN:

1441272

Hom.:

Cov.:

AF XY:

0.0000952

AC XY:

AN XY:

714558

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33248

American (AMR)

AF:

0.00

AC:

AN:

41854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25672

East Asian (EAS)

AF:

0.00324

AC:

127

AN:

39206

South Asian (SAS)

AF:

0.00

AC:

AN:

82476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101100

Other (OTH)

AF:

0.000101

AC:

AN:

59692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41538

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00522

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000287

ExAC

AF:

0.000274

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.077

MetaRNN

Benign

0.014

MetaSVM

Uncertain

0.32

PhyloP100

7.6

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.56

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0010

Vest4

0.85

MutPred

0.53

Gain of catalytic residue at P366 (P = 0.089)

MVP

0.63

MPC

0.19

ClinPred

0.15

GERP RS

5.5

gMVP

0.58

Mutation Taster

=46/54

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over