Variant 11-56469630-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001004742.3(OR5M3):c.868C>A(p.Leu290Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,385,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

OR5M3
NM_001004742.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.221

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38695973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5M3	NM_001004742.3 link	c.868C>A	p.Leu290Met	missense_variant	2/2	ENST00000641993.1	NP_001004742.2	Q8NGP4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5M3	ENST00000641993.1 link	c.868C>A	p.Leu290Met	missense_variant	2/2	NM_001004742.3	ENSP00000493070.1	Q8NGP4
ENSG00000284732	ENST00000641310.1 link	c.144+724C>A		intron_variant			ENSP00000493052.1	A0A286YEX6
ENSG00000284732	ENST00000641599.1 link	c.144+724C>A		intron_variant			ENSP00000493241.1	A0A286YF13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000541

AC:

AN:

184834

Hom.:

AF XY:

0.00

AC XY:

AN XY:

98490

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000216

AC:

AN:

1385732

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000281

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.868C>A (p.L290M) alteration is located in exon 1 (coding exon 1) of the OR5M3 gene. This alteration results from a C to A substitution at nucleotide position 868, causing the leucine (L) at amino acid position 290 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0056

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.7

.;N

REVEL

Benign

0.20

Sift

Uncertain

0.0060

.;D

Sift4G

Uncertain

0.016

.;D

Polyphen

1.0

D;D

Vest4

0.37

MutPred

0.63

Gain of disorder (P = 0.0379);Gain of disorder (P = 0.0379);

MVP

0.38

MPC

0.34

ClinPred

0.29

GERP RS

2.2

Varity_R

0.27

gMVP

0.041

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over