Variant chr3-161503196-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001080440.1(OTOL1):c.688G>A(p.Gly230Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,455,258 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000061 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00013 ( 4 hom. )

Consequence

OTOL1
NM_001080440.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0750

Variant links:

Genes affected

OTOL1 (HGNC:34071): (otolin 1) This gene encodes a secreted glycoprotein with a C-terminal complement Cq1-like globular domain that belongs to the C1q/tumor necrosis factor-related protein (CTRP) family. The encoded protein is expressed in the inner ear and forms a multimeric complex called the otoconia, together with cerebellin-1 and otoconin-90, as part of the otoconial membrane. It contains extensive posttranslational modifications including hydroxylated prolines and glycosylated lysines. Naturally occurring mutations in this gene are associated with abnormal otoconia formation and balance deficits resulting from vestibular dysfunction. [provided by RefSeq, Jul 2017]

OTOL1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOL1	NM_001080440.1 linkuse as main transcript	c.688G>A	p.Gly230Arg	missense_variant	4/4	ENST00000327928.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOL1	ENST00000327928.4 linkuse as main transcript	c.688G>A	p.Gly230Arg	missense_variant	4/4	2	NM_001080440.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000606

AC:

AN:

148506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000671

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00179

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000128

AC:

AN:

78364

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

38892

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:

0.00148

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000135

AC:

176

AN:

1306638

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

128

AN XY:

634640

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000997

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00274

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.64e-7

Gnomad4 OTH exome

AF:

0.0000370

GnomAD4 genome

AF:

0.0000606

AC:

AN:

148620

Hom.:

Cov.:

AF XY:

0.0000829

AC XY:

AN XY:

72402

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000670

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00179

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000147

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.41

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.49

MetaSVM

Pathogenic

1.2

MutationAssessor

Pathogenic

4.1

MutationTaster

Benign

0.84

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.52

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Vest4

0.12

MutPred

0.95

Gain of solvent accessibility (P = 1e-04);

MVP

0.78

MPC

0.022

ClinPred

0.47

Varity_R

0.27

gMVP

0.46

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over