Variant 6-29112746-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_001005216.4(OR2J3):c.856C>T(p.Pro286Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,613,542 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

OR2J3
NM_001005216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

Variant links:

Genes affected

OR2J3 (HGNC:8261): (olfactory receptor family 2 subfamily J member 3) This gene encodes a G-protein-coupled receptor (GPCR) that functions as an olfactory receptor. Olfactory receptors interact with odorant molecules in the nose to initiate a neuronal response that triggers the perception of a smell. The protein encoded by this gene responds to cis-3-hexen-1-ol, which is released by wounded plants, including cut grass. This gene is situated in a cluster of similar olfactory-receptor coding genes on chromosome 6. [provided by RefSeq, May 2013]

OR2J3 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=0.15016538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2J3	NM_001005216.4 linkuse as main transcript	c.856C>T	p.Pro286Ser	missense_variant	4/4	ENST00000641151.2	NP_001005216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	Appris
OR2J3	ENST00000641151.2 linkuse as main transcript	c.856C>T	p.Pro286Ser	missense_variant	4/4	NM_001005216.4	ENSP00000492961	P1
OR2J3	ENST00000377169.2 linkuse as main transcript	c.856C>T	p.Pro286Ser	missense_variant	1/1		ENSP00000366374	P1
OR2J3	ENST00000641960.1 linkuse as main transcript	c.856C>T	p.Pro286Ser	missense_variant	5/5		ENSP00000493439	P1

Frequencies

GnomAD3 genomes

AF:

0.000409

AC:

AN:

151650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000707

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.000510

AC:

127

AN:

248818

Hom.:

AF XY:

0.000615

AC XY:

AN XY:

135010

show subpopulations

Gnomad AFR exome

AF:

0.0000650

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000630

Gnomad OTH exome

AF:

0.000828

GnomAD4 exome

AF:

0.000465

AC:

679

AN:

1461774

Hom.:

Cov.:

AF XY:

0.000487

AC XY:

354

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000475

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.000409

AC:

AN:

151768

Hom.:

Cov.:

AF XY:

0.000445

AC XY:

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000707

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000917

Hom.:

Bravo

AF:

0.000495

ESP6500AA

AF:

0.000811

AC:

ESP6500EA

AF:

0.000197

AC:

ExAC

AF:

0.000488

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00101

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

Mar 21, 2024

The c.856C>T (p.P286S) alteration is located in exon 1 (coding exon 1) of the OR2J3 gene. This alteration results from a C to T substitution at nucleotide position 856, causing the proline (P) at amino acid position 286 to be replaced by a serine (S). 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

0.30

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

.;.;D

M_CAP

Benign

0.0010

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.82

MutationTaster

Benign

0.99

PrimateAI

Benign

0.20

PROVEAN

Pathogenic

-7.7

.;.;D

REVEL

Benign

0.17

Sift

Pathogenic

0.0

.;.;D

Sift4G

Uncertain

0.031

.;.;D

Vest4

0.34

MVP

0.57

MPC

0.54

ClinPred

0.19

GERP RS

3.0

gMVP

0.14

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