chr11-56137069-G-C

Variant names:

• chr11-56137069-G-C
• rs768740274
• NM_001004064.2:c.650C>G

Variant summary

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

The NM_001004064.2(OR8J3):​c.650C>G​(p.Ser217Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR8J3 NM_001004064.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.20
• Publications: 6 publications found

Genes affected

OR8J3 (HGNC:15312): (olfactory receptor family 8 subfamily J member 3) Predicted to enable odorant binding activity and olfactory receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and sensory perception of smell. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
OR8J3	NM_001004064.2	c.650C>G	p.Ser217Cys	missense_variant	Exon 2 of 2	ENST00000642058.1	NP_001004064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR8J3	ENST00000642058.1	c.650C>G	p.Ser217Cys	missense_variant	Exon 2 of 2		NM_001004064.2	ENSP00000493166.1
OR8J3	ENST00000641913.1	c.650C>G	p.Ser217Cys	missense_variant	Exon 2 of 2			ENSP00000493417.1
OR8J3	ENST00000641489.1	n.30-31C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250932 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.650C>G (p.S217C) alteration is located in exon 1 (coding exon 1) of the OR8J3 gene. This alteration results from a C to G substitution at nucleotide position 650, causing the serine (S) at amino acid position 217 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	0.20
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T;T;T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	.;.;T
M_CAP	Benign	0.0036	T
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Pathogenic	4.0	H;H;H
PhyloP100		4.2
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.8	.;.;D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	.;.;D
Sift4G	Pathogenic	0.0	.;.;D
Polyphen		1.0	D;D;D
Vest4		0.44
MutPred		0.65		Loss of MoRF binding (P = 0.178);Loss of MoRF binding (P = 0.178);Loss of MoRF binding (P = 0.178);
MVP		0.62
MPC		0.016
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.87
gMVP		0.36
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs768740274; hg19: chr11-55904545;