rs17350764

Variant names:

• chr11-5047201-G-A
• rs17350764
• NM_001001916.2:c.676G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001916.2(OR52J3):​c.676G>A​(p.Val226Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,610,390 control chromosomes in the GnomAD database, including 32,853 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3584 hom., cov: 26)
  • Exomes 𝑓: 0.20 (29269 hom.)
• Consequence: OR52J3 NM_001001916.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 24 publications found

Genes affected

OR52J3 (HGNC:14799): (olfactory receptor family 52 subfamily J member 3) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062103868).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001916.2. 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
	OR52J3	NM_001001916.2	MANE Select	c.676G>A	p.Val226Ile	missense	Exon 1 of 1	NP_001001916.2	Q8NH60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52J3	ENST00000380370.1	TSL:6 MANE Select	c.676G>A	p.Val226Ile	missense	Exon 1 of 1	ENSP00000369728.1	Q8NH60

Frequencies

GnomAD3 genomes AF: 0.212 AC: 31553 AN: 148564 Hom.: 3576 Cov.: 26

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.226

GnomAD2 exomes AF: 0.216 AC: 54301 AN: 251232 AF XY: 0.214

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.124

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.196 AC: 286561 AN: 1461708 Hom.: 29269 Cov.: 43 AF XY: 0.198 AC XY: 143716 AN XY: 727148

African (AFR) AF: 0.243 AC: 8132 AN: 33458

American (AMR) AF: 0.346 AC: 15486 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5834 AN: 26130

East Asian (EAS) AF: 0.124 AC: 4926 AN: 39696

South Asian (SAS) AF: 0.258 AC: 22247 AN: 86254

European-Finnish (FIN) AF: 0.144 AC: 7679 AN: 53416

Middle Eastern (MID) AF: 0.223 AC: 1287 AN: 5764

European-Non Finnish (NFE) AF: 0.188 AC: 208687 AN: 1111882

Other (OTH) AF: 0.203 AC: 12283 AN: 60394

GnomAD4 genome AF: 0.212 AC: 31594 AN: 148682 Hom.: 3584 Cov.: 26 AF XY: 0.213 AC XY: 15405 AN XY: 72256

African (AFR) AF: 0.250 AC: 10008 AN: 40078

American (AMR) AF: 0.304 AC: 4458 AN: 14662

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 816 AN: 3452

East Asian (EAS) AF: 0.114 AC: 579 AN: 5074

South Asian (SAS) AF: 0.249 AC: 1137 AN: 4562

European-Finnish (FIN) AF: 0.144 AC: 1468 AN: 10226

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12454 AN: 67374

Other (OTH) AF: 0.224 AC: 460 AN: 2052

Alfa AF: 0.199 Hom.: 9566

Bravo AF: 0.226

TwinsUK AF: 0.177 AC: 655

ALSPAC AF: 0.183 AC: 705

ESP6500AA AF: 0.245 AC: 1079

ESP6500EA AF: 0.187 AC: 1605

ExAC AF: 0.211 AC: 25639

Asia WGS AF: 0.179 AC: 622 AN: 3478

EpiCase AF: 0.183

EpiControl AF: 0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.078
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.051
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.046
Sift	Benign	0.033	D
Sift4G	Uncertain	0.046	D
Polyphen		0.98	D
Vest4		0.035
MPC		0.016
ClinPred		0.011	T
GERP RS		3.3
Varity_R		0.087
gMVP		0.049
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17350764; hg19: chr11-5068431; COSMIC: COSV66746780;