Genetic Variant OR2J3:p.Lys298Glu (chr6-29112782-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005216.4(OR2J3):c.892A>G(p.Lys298Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,378 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K298R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

OR2J3
NM_001005216.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.256

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21197659).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2J3	NM_001005216.4	MANE Select	c.892A>G	p.Lys298Glu	missense	Exon 4 of 4	NP_001005216.2	A0A126GWT2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR2J3	ENST00000641151.2	MANE Select	c.892A>G	p.Lys298Glu	missense	Exon 4 of 4	ENSP00000492961.1	A0A126GWT2
OR2J3	ENST00000377169.2	TSL:6	c.892A>G	p.Lys298Glu	missense	Exon 1 of 1	ENSP00000366374.1	O76001
OR2J3	ENST00000641960.1		c.892A>G	p.Lys298Glu	missense	Exon 5 of 5	ENSP00000493439.1	A0A126GWT2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000807

AC:

AN:

247696

AF XY:

0.0000149

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461378

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111624

Other (OTH)

AF:

0.0000166

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.022

Eigen_PC

Benign

-0.084

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.76

M_CAP

Benign

0.0020

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.92

PhyloP100

0.26

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.095

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.012

Vest4

0.28

MutPred

0.44

Loss of methylation at K298 (P = 0.0011)

MVP

0.38

MPC

0.53

ClinPred

0.95

GERP RS

3.0

gMVP

0.11

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over