Variant 2-240045787-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_173351.2(OR6B3):c.286G>A(p.Gly96Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,482,458 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000086 ( 1 hom. )

Consequence

OR6B3
NM_173351.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.814

Variant links:

Genes affected

OR6B3 (HGNC:15042): (olfactory receptor family 6 subfamily B member 3) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR6B3 links:

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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=0.081416816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6B3	NM_173351.2 linkuse as main transcript	c.286G>A	p.Gly96Arg	missense_variant	3/3	ENST00000641019.2	NP_775486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6B3	ENST00000641019.2 linkuse as main transcript	c.286G>A	p.Gly96Arg	missense_variant	3/3		NM_173351.2	ENSP00000493035	P1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000366

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000957

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.000147

AC:

AN:

244640

Hom.:

AF XY:

0.000136

AC XY:

AN XY:

132836

show subpopulations

Gnomad AFR exome

AF:

0.000789

Gnomad AMR exome

AF:

0.000176

Gnomad ASJ exome

AF:

0.000821

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000813

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000864

AC:

115

AN:

1331258

Hom.:

Cov.:

AF XY:

0.0000912

AC XY:

AN XY:

669136

show subpopulations

Gnomad4 AFR exome

AF:

0.000583

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.000865

Gnomad4 EAS exome

AF:

0.000231

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000483

Gnomad4 OTH exome

AF:

0.000125

GnomAD4 genome

AF:

0.000132

AC:

AN:

151200

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

73810

show subpopulations

Gnomad4 AFR

AF:

0.000365

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000957

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000288

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000808

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.000149

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.286G>A (p.G96R) alteration is located in exon 1 (coding exon 1) of the OR6B3 gene. This alteration results from a G to A substitution at nucleotide position 286, causing the glycine (G) at amino acid position 96 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

0.33

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.79

T;.

M_CAP

Benign

0.0010

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-4.9

D;.

REVEL

Benign

0.14

Sift

Uncertain

0.020

D;.

Sift4G

Uncertain

0.031

D;.

Polyphen

0.75

P;P

Vest4

0.44

MutPred

0.63

Gain of MoRF binding (P = 0.0544);Gain of MoRF binding (P = 0.0544);

MVP

0.37

MPC

1.1

ClinPred

0.091

GERP RS

4.0

Varity_R

0.62

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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