chr12-80367631-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000547103.7(OTOGL):c.6402G>T(p.Leu2134Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,534,542 control chromosomes in the GnomAD database, including 28,595 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2746 hom., cov: 31)

Exomes 𝑓: 0.19 ( 25849 hom. )

Consequence

OTOGL
ENST00000547103.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.51

Publications

14 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: 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

OTOGL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0016458333).

BP6

Variant 12-80367631-G-T is Benign according to our data. Variant chr12-80367631-G-T is described in ClinVar as Benign. ClinVar VariationId is 226968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000547103.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OTOGL	NM_001378609.3	MANE Select	c.6402G>T	p.Leu2134Phe	missense	Exon 54 of 59	NP_001365538.2
OTOGL	NM_001378610.3		c.6402G>T	p.Leu2134Phe	missense	Exon 57 of 62	NP_001365539.2
OTOGL	NM_173591.7		c.6402G>T	p.Leu2134Phe	missense	Exon 54 of 59	NP_775862.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OTOGL	ENST00000547103.7	TSL:5 MANE Select	c.6402G>T	p.Leu2134Phe	missense	Exon 54 of 59	ENSP00000447211.2
OTOGL	ENST00000646859.1		c.6267G>T	p.Leu2089Phe	missense	Exon 58 of 63	ENSP00000496036.1
OTOGL	ENST00000298820.7	TSL:5	c.1596G>T	p.Leu532Phe	missense	Exon 13 of 18	ENSP00000298820.3

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

28026

AN:

151918

Hom.:

2745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.0430

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.190

GnomAD2 exomes

AF:

0.165

AC:

30205

AN:

182930

AF XY:

0.168

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.0364

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.189

AC:

261337

AN:

1382506

Hom.:

25849

Cov.:

AF XY:

0.190

AC XY:

130110

AN XY:

685990

show subpopulations

African (AFR)

AF:

0.171

AC:

5241

AN:

30586

American (AMR)

AF:

0.192

AC:

6873

AN:

35810

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4483

AN:

24346

East Asian (EAS)

AF:

0.0343

AC:

1290

AN:

37574

South Asian (SAS)

AF:

0.205

AC:

16031

AN:

78102

European-Finnish (FIN)

AF:

0.109

AC:

5625

AN:

51510

Middle Eastern (MID)

AF:

0.214

AC:

1190

AN:

5560

European-Non Finnish (NFE)

AF:

0.198

AC:

210031

AN:

1061622

Other (OTH)

AF:

0.184

AC:

10573

AN:

57396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

9182

18363

27545

36726

45908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7294

14588

21882

29176

36470

<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:

0.184

AC:

28028

AN:

152036

Hom.:

2746

Cov.:

AF XY:

0.181

AC XY:

13484

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.181

AC:

7507

AN:

41472

American (AMR)

AF:

0.216

AC:

3286

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

639

AN:

3464

East Asian (EAS)

AF:

0.0431

AC:

223

AN:

5176

South Asian (SAS)

AF:

0.216

AC:

1039

AN:

4820

European-Finnish (FIN)

AF:

0.107

AC:

1132

AN:

10592

Middle Eastern (MID)

AF:

0.223

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.198

AC:

13483

AN:

67962

Other (OTH)

AF:

0.188

AC:

397

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1172

2344

3515

4687

5859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.191

Hom.:

7673

Bravo

AF:

0.192

TwinsUK

AF:

0.193

AC:

715

ALSPAC

AF:

0.199

AC:

766

ESP6500AA

AF:

0.183

AC:

807

ESP6500EA

AF:

0.192

AC:

1648

ExAC

AF:

0.160

AC:

19275

Asia WGS

AF:

0.139

AC:

482

AN:

3470

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

PhyloP100

1.5

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

REVEL

Benign

0.026

Sift

Benign

0.58

Sift4G

Benign

0.24

Vest4

0.13

MPC

0.023

ClinPred

0.0016

GERP RS

2.7

PromoterAI

0.0028

Neutral

(source)

gMVP

0.42

Mutation Taster

=90/10

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over