NM_001001916.2:c.245G>T

Variant names:

• chr11-5046770-G-T
• rs570638059
• NM_001001916.2:c.245G>T

Variant summary

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

The NM_001001916.2(OR52J3):​c.245G>T​(p.Arg82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: OR52J3 NM_001001916.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 1 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: 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=0.24567628).

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.245G>T	p.Arg82Leu	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.245G>T	p.Arg82Leu	missense	Exon 1 of 1	ENSP00000369728.1	Q8NH60

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151952 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461768 Hom.: 0 Cov.: 58 AF XY: 0.00000550 AC XY: 4 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111956

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151952 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74204

African (AFR) AF: 0.00 AC: 0 AN: 41354

American (AMR) AF: 0.0000656 AC: 1 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.12
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.051
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.90	P
Vest4		0.49
MutPred		0.42		Gain of glycosylation at T77 (P = 0.1336)
MVP		0.25
MPC		0.049
ClinPred		0.96	D
GERP RS		1.3
PromoterAI		-0.0044	Neutral
Varity_R		0.30
gMVP		0.47
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: rs570638059; hg19: chr11-5068000; COSMIC: COSV104702619;