Variant 8-132024507-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080399.3(OC90):c.1408G>A(p.Gly470Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

OC90
NM_001080399.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

Variant links:

Genes affected

OC90 (HGNC:8100): (otoconin 90) Predicted to enable calcium ion binding activity and structural molecule activity. Predicted to be involved in otolith mineralization. Predicted to be located in extracellular region. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

OC90 links:

ENSG00000258417 (HGNC:):

ENSG00000258417 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12664166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OC90	NM_001080399.3 link	c.1408G>A	p.Gly470Arg	missense_variant	Exon 14 of 14	ENST00000254627.4	NP_001073868.2	Q02509-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OC90	ENST00000254627.4 link	c.1408G>A	p.Gly470Arg	missense_variant	Exon 14 of 14	2	NM_001080399.3	ENSP00000254627.3		Q02509-1
ENSG00000258417	ENST00000262283.5 link	c.2044G>A	p.Gly682Arg	missense_variant	Exon 18 of 18	5		ENSP00000262283.5		I6L893

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000438

AC:

AN:

228222

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123678

show subpopulations

Gnomad AFR exome

AF:

0.0000667

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426620

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1408G>A (p.G470R) alteration is located in exon 14 (coding exon 13) of the OC90 gene. This alteration results from a G to A substitution at nucleotide position 1408, causing the glycine (G) at amino acid position 470 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.095

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.22

T;T

Vest4

0.23

MVP

0.39

MPC

0.0043

ClinPred

0.17

GERP RS

5.0

Varity_R

0.068

gMVP

0.31

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over