6-29112134-C-T

Position:

• chr6-29112134-C-T

Variant summary

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

The NM_001005216.4(OR2J3):​c.244C>T​(p.Pro82Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2J3 NM_001005216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.41

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]

ACMG classification

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/exons	MANE	Protein	UniProt
OR2J3	NM_001005216.4	c.244C>T	p.Pro82Ser	missense_variant	4/4	ENST00000641151.2	NP_001005216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2J3	ENST00000641151.2	c.244C>T	p.Pro82Ser	missense_variant	4/4		NM_001005216.4	ENSP00000492961.1
OR2J3	ENST00000377169.2	c.244C>T	p.Pro82Ser	missense_variant	1/1	6		ENSP00000366374.1
OR2J3	ENST00000641960.1	c.244C>T	p.Pro82Ser	missense_variant	5/5			ENSP00000493439.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 10, 2024

The c.244C>T (p.P82S) 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 244, causing the proline (P) at amino acid position 82 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	.;.;D
M_CAP	Benign	0.00094	T
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-7.9	.;.;D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	.;.;D
Sift4G	Uncertain	0.0090	.;.;D
Vest4		0.54
MutPred		0.61		Loss of glycosylation at S79 (P = 0.3552);Loss of glycosylation at S79 (P = 0.3552);Loss of glycosylation at S79 (P = 0.3552);
MVP		0.57
MPC		0.51
ClinPred		1.0	D
GERP RS		2.8
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-29079911; COSMIC: COSV101013673;