Genetic Variant OR5M3:p.Leu283Phe (chr11-56469649-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001004742.3(OR5M3):c.849G>C(p.Leu283Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000495 in 1,415,074 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

OR5M3
NM_001004742.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.84

Publications

0 publications found

Variant links:

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]

OR5M3 links:

ENSG00000284732 (HGNC:):

ENSG00000284732 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.849G>C	p.Leu283Phe	missense	Exon 2 of 2	NP_001004742.2	Q8NGP4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR5M3	ENST00000641993.1	MANE Select	c.849G>C	p.Leu283Phe	missense	Exon 2 of 2	ENSP00000493070.1	Q8NGP4
ENSG00000284732	ENST00000641310.1		c.144+705G>C		intron	N/A	ENSP00000493052.1	A0A286YEX6
ENSG00000284732	ENST00000641599.1		c.144+705G>C		intron	N/A	ENSP00000493241.1	A0A286YF13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000495

AC:

AN:

1415074

Hom.:

Cov.:

AF XY:

0.00000998

AC XY:

AN XY:

701096

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32210

American (AMR)

AF:

0.00

AC:

AN:

41240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24070

East Asian (EAS)

AF:

0.00

AC:

AN:

39138

South Asian (SAS)

AF:

0.00

AC:

AN:

81390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5572

European-Non Finnish (NFE)

AF:

0.00000555

AC:

AN:

1080640

Other (OTH)

AF:

0.0000171

AC:

AN:

58382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0098

Eigen

Benign

0.015

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.84

M_CAP

Benign

0.0093

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.3

PhyloP100

-2.8

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.13

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.39

MutPred

0.70

Loss of catalytic residue at L283 (P = 0.002)

MVP

0.52

MPC

0.15

ClinPred

0.93

GERP RS

2.7

Varity_R

0.61

gMVP

0.068

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over