6-29112698-T-G

Position:

• chr6-29112698-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005216.4(OR2J3):​c.808T>G​(p.Ser270Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 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: -1.77

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18024707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2J3	NM_001005216.4	c.808T>G	p.Ser270Ala	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.808T>G	p.Ser270Ala	missense_variant	4/4		NM_001005216.4	ENSP00000492961	P1
OR2J3	ENST00000377169.2	c.808T>G	p.Ser270Ala	missense_variant	1/1			ENSP00000366374	P1
OR2J3	ENST00000641960.1	c.808T>G	p.Ser270Ala	missense_variant	5/5			ENSP00000493439	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jan 05, 2022

The c.808T>G (p.S270A) alteration is located in exon 1 (coding exon 1) of the OR2J3 gene. This alteration results from a T to G substitution at nucleotide position 808, causing the serine (S) at amino acid position 270 to be replaced by an alanine (A). 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	0.091
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.64	.;.;T
M_CAP	Benign	0.00052	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.3	.;.;N
REVEL	Benign	0.045
Sift	Benign	0.13	.;.;T
Sift4G	Benign	0.16	.;.;T
Vest4		0.049
MutPred		0.48		Gain of catalytic residue at S270 (P = 0.0419);Gain of catalytic residue at S270 (P = 0.0419);Gain of catalytic residue at S270 (P = 0.0419);
MVP		0.20
MPC		0.11
ClinPred		0.29	T
GERP RS		0.43
gMVP		0.031

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: chr6-29080475;