11-56470011-C-T

Variant names:

• chr11-56470011-C-T
• rs17150664
• NM_001004742.3:c.487G>A

Variant summary

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

The NM_001004742.3(OR5M3):​c.487G>A​(p.Gly163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,613,518 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G163C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0032 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (83 hom.)
• Consequence: OR5M3 NM_001004742.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688
• Publications: 9 publications found

Genes affected

OR5M3 (HGNC:14806): (olfactory receptor family 5 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]

ENSG00000284732 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018546283).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004742.3. 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
	OR5M3	NM_001004742.3	MANE Select	c.487G>A	p.Gly163Ser	missense	Exon 2 of 2	NP_001004742.2	Q8NGP4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5M3	ENST00000641993.1	MANE Select	c.487G>A	p.Gly163Ser	missense	Exon 2 of 2	ENSP00000493070.1	Q8NGP4
	ENSG00000284732	ENST00000641310.1		c.144+343G>A		intron	N/A	ENSP00000493052.1	A0A286YEX6
	ENSG00000284732	ENST00000641599.1		c.144+343G>A		intron	N/A	ENSP00000493241.1	A0A286YF13

Frequencies

GnomAD3 genomes AF: 0.00325 AC: 493 AN: 151906 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0763

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00199

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00241

GnomAD2 exomes AF: 0.00643 AC: 1616 AN: 251210 AF XY: 0.00588

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0801

Gnomad FIN exome AF: 0.00250

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00185 AC: 2711 AN: 1461494 Hom.: 83 Cov.: 33 AF XY: 0.00178 AC XY: 1295 AN XY: 727070

African (AFR) AF: 0.000239 AC: 8 AN: 33472

American (AMR) AF: 0.000157 AC: 7 AN: 44718

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

East Asian (EAS) AF: 0.0504 AC: 1999 AN: 39696

South Asian (SAS) AF: 0.00119 AC: 103 AN: 86244

European-Finnish (FIN) AF: 0.00318 AC: 170 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000139 AC: 154 AN: 1111670

Other (OTH) AF: 0.00444 AC: 268 AN: 60378

GnomAD4 genome AF: 0.00321 AC: 488 AN: 152024 Hom.: 14 Cov.: 32 AF XY: 0.00366 AC XY: 272 AN XY: 74306

African (AFR) AF: 0.000602 AC: 25 AN: 41508

American (AMR) AF: 0.00105 AC: 16 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.0753 AC: 390 AN: 5180

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4812

European-Finnish (FIN) AF: 0.00199 AC: 21 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67952

Other (OTH) AF: 0.00286 AC: 6 AN: 2100

Alfa AF: 0.00174 Hom.: 15

Bravo AF: 0.00347

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00583 AC: 708

Asia WGS AF: 0.0260 AC: 89 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.055	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-0.69
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.80	N
REVEL	Benign	0.10
Sift	Benign	0.45	T
Sift4G	Benign	0.75	T
Polyphen		0.33	B
Vest4		0.079
MVP		0.24
MPC		0.063
ClinPred		0.010	T
GERP RS		4.3
Varity_R		0.071
gMVP		0.11
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: rs17150664; hg19: chr11-56237487; COSMIC: COSV107347678;