rs747404277

Variant names:

• chr1-248203548-G-A
• rs747404277
• NM_001004689.2:c.481G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004689.2(OR2M3):​c.481G>A​(p.Val161Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,613,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: OR2M3 NM_001004689.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.16
• Publications: 1 publications found

Genes affected

OR2M3 (HGNC:8269): (olfactory receptor family 2 subfamily M 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07449666).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004689.2. 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
	OR2M3	NM_001004689.2	MANE Select	c.481G>A	p.Val161Ile	missense	Exon 2 of 2	NP_001004689.1	Q8NG83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2M3	ENST00000641626.1	MANE Select	c.481G>A	p.Val161Ile	missense	Exon 2 of 2	ENSP00000492981.1	Q8NG83
	OR2M3	ENST00000456743.3	TSL:6	c.481G>A	p.Val161Ile	missense	Exon 1 of 1	ENSP00000389625.1	Q8NG83

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151968 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 250906 AF XY: 0.0000148

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: 0.0000441

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000118 AC: 172 AN: 1461622 Hom.: 0 Cov.: 34 AF XY: 0.0000990 AC XY: 72 AN XY: 727126

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000144 AC: 160 AN: 1111818

Other (OTH) AF: 0.000199 AC: 12 AN: 60378

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151968 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74220

African (AFR) AF: 0.00 AC: 0 AN: 41344

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

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	0.083
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.1
DANN	Benign	0.90
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.065	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.91	L
PhyloP100		-3.2
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.0090
Sift	Benign	0.13	T
Sift4G	Benign	0.57	T
Polyphen		0.028	B
Vest4		0.051
MutPred		0.19		Gain of loop (P = 0.2754)
MVP		0.26
MPC		0.052
ClinPred		0.039	T
GERP RS		0.53
Varity_R		0.056
gMVP		0.020
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747404277; hg19: chr1-248366850;