6-29112263-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001005216.4(OR2J3):​c.373C>T​(p.Arg125Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

OR2J3
NM_001005216.4 missense

Scores

1
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.527
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR2J3NM_001005216.4 linkc.373C>T p.Arg125Cys missense_variant Exon 4 of 4 ENST00000641151.2 NP_001005216.2 O76001A0A126GWT2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR2J3ENST00000641151.2 linkc.373C>T p.Arg125Cys missense_variant Exon 4 of 4 NM_001005216.4 ENSP00000492961.1 A0A126GWT2
OR2J3ENST00000377169.2 linkc.373C>T p.Arg125Cys missense_variant Exon 1 of 1 6 ENSP00000366374.1 O76001
OR2J3ENST00000641960.1 linkc.373C>T p.Arg125Cys missense_variant Exon 5 of 5 ENSP00000493439.1 A0A126GWT2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152108
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249296
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135270
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461872
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152226
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.373C>T (p.R125C) 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 373, causing the arginine (R) at amino acid position 125 to be replaced by a cysteine (C). 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
0.15
BayesDel_addAF
Benign
-0.012
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
21
DANN
Uncertain
0.99
Eigen
Uncertain
0.32
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.50
D
LIST_S2
Uncertain
0.87
.;.;D
M_CAP
Benign
0.0094
T
MetaRNN
Uncertain
0.50
D;D;D
MetaSVM
Uncertain
0.38
D
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-7.1
.;.;D
REVEL
Uncertain
0.57
Sift
Uncertain
0.018
.;.;D
Sift4G
Uncertain
0.019
.;.;D
Vest4
0.16
MutPred
0.51
Gain of catalytic residue at S122 (P = 0.3004);Gain of catalytic residue at S122 (P = 0.3004);Gain of catalytic residue at S122 (P = 0.3004);
MVP
0.79
MPC
0.21
ClinPred
0.77
D
GERP RS
2.6
gMVP
0.59

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.

Other links and lift over

dbSNP: rs781677754; hg19: chr6-29080040; COSMIC: COSV65849624; API