6-29111967-T-C

Position:

• chr6-29111967-T-C

Variant summary

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

The NM_001005216.4(OR2J3):​c.77T>C​(p.Leu26Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2J3 NM_001005216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.760

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.77T>C	p.Leu26Pro	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.77T>C	p.Leu26Pro	missense_variant	4/4		NM_001005216.4	ENSP00000492961	P1
OR2J3	ENST00000377169.2	c.77T>C	p.Leu26Pro	missense_variant	1/1			ENSP00000366374	P1
OR2J3	ENST00000641960.1	c.77T>C	p.Leu26Pro	missense_variant	5/5			ENSP00000493439	P1

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

Apr 28, 2023

The c.77T>C (p.L26P) alteration is located in exon 1 (coding exon 1) of the OR2J3 gene. This alteration results from a T to C substitution at nucleotide position 77, causing the leucine (L) at amino acid position 26 to be replaced by a proline (P). 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	0.29
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Benign	0.16
Eigen_PC	Benign	-0.099
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.58	.;.;T
M_CAP	Benign	0.00096	T
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.93	N
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-6.7	.;.;D
REVEL	Benign	0.10
Sift	Pathogenic	0.0	.;.;D
Sift4G	Pathogenic	0.0010	.;.;D
Vest4		0.69
MutPred		0.70		Loss of stability (P = 0.0875);Loss of stability (P = 0.0875);Loss of stability (P = 0.0875);
MVP		0.39
MPC		0.65
ClinPred		0.97	D
GERP RS		3.0
gMVP		0.30

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: chr6-29079744;