Genetic Variant NM_001004742.3:c.899T>A (chr11-56469599-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004742.3(OR5M3):c.899T>A(p.Met300Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000295 in 1,353,784 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. 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. M300T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

OR5M3
NM_001004742.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -9.77

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027510196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5M3	NM_001004742.3 link	c.899T>A	p.Met300Lys	missense_variant	Exon 2 of 2	ENST00000641993.1	NP_001004742.2	Q8NGP4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5M3	ENST00000641993.1 link	c.899T>A	p.Met300Lys	missense_variant	Exon 2 of 2	NM_001004742.3	ENSP00000493070.1	Q8NGP4
ENSG00000284732	ENST00000641310.1 link	c.144+755T>A		intron_variant	Intron 2 of 3		ENSP00000493052.1	A0A286YEX6
ENSG00000284732	ENST00000641599.1 link	c.144+755T>A		intron_variant	Intron 2 of 2		ENSP00000493241.1	A0A286YF13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000221

AC:

AN:

180602

AF XY:

0.0000104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000143

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000246

GnomAD4 exome

AF:

0.00000295

AC:

AN:

1353784

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

666570

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29890

American (AMR)

AF:

0.0000998

AC:

AN:

30072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20698

East Asian (EAS)

AF:

0.00

AC:

AN:

38724

South Asian (SAS)

AF:

0.00

AC:

AN:

72202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1050740

Other (OTH)

AF:

0.0000179

AC:

AN:

55718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.0010

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.0015

T;T

Eigen

Benign

-2.5

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.00036

LIST_S2

Benign

0.015

.;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

N;N

PhyloP100

-9.8

PrimateAI

Benign

0.19

PROVEAN

Benign

2.9

.;N

REVEL

Benign

0.046

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0

B;B

Vest4

0.16

MutPred

0.46

Gain of disorder (P = 0.0154);Gain of disorder (P = 0.0154);

MVP

0.055

MPC

0.079

ClinPred

0.046

GERP RS

-10

Varity_R

0.10

gMVP

0.12

Mutation Taster

=93/7

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over