rs777661564

Variant names:

• chr6-29112782-A-C
• rs777661564
• NM_001005216.4:c.892A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-29112782-A-C
• chr6-29112782-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005216.4(OR2J3):​c.892A>C​(p.Lys298Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 0.0000014 (0 hom.)
• Consequence: OR2J3 NM_001005216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.256
• Publications: 1 publications found

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

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=0.1681441).

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>C	p.Lys298Gln	missense	Exon 4 of 4	NP_001005216.2	A0A126GWT2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2J3	ENST00000641151.2	MANE Select	c.892A>C	p.Lys298Gln	missense	Exon 4 of 4	ENSP00000492961.1	A0A126GWT2
	OR2J3	ENST00000377169.2	TSL:6	c.892A>C	p.Lys298Gln	missense	Exon 1 of 1	ENSP00000366374.1	O76001
	OR2J3	ENST00000641960.1		c.892A>C	p.Lys298Gln	missense	Exon 5 of 5	ENSP00000493439.1	A0A126GWT2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461378 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727000

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111624

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.97
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.26
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.057
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.031	D
Vest4		0.093
MutPred		0.44		Loss of methylation at K298 (P = 0.0011)
MVP		0.38
MPC		0.48
ClinPred		0.94	D
GERP RS		3.0
gMVP		0.097
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs777661564; hg19: chr6-29080559;