Variant 11-56469649-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004742.3(OR5M3):c.849G>T(p.Leu283Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,567,312 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

OR5M3
NM_001004742.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.84

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0339624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5M3	NM_001004742.3 linkuse as main transcript	c.849G>T	p.Leu283Phe	missense_variant	2/2	ENST00000641993.1	NP_001004742.2	Q8NGP4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5M3	ENST00000641993.1 linkuse as main transcript	c.849G>T	p.Leu283Phe	missense_variant	2/2	NM_001004742.3	ENSP00000493070.1	Q8NGP4
ENSG00000284732	ENST00000641310.1 linkuse as main transcript	c.144+705G>T		intron_variant			ENSP00000493052.1	A0A286YEX6
ENSG00000284732	ENST00000641599.1 linkuse as main transcript	c.144+705G>T		intron_variant			ENSP00000493241.1	A0A286YF13

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

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:

0.000132

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000265

AC:

AN:

203570

Hom.:

AF XY:

0.000247

AC XY:

AN XY:

109140

show subpopulations

Gnomad AFR exome

AF:

0.000350

Gnomad AMR exome

AF:

0.00123

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:

0.000148

Gnomad OTH exome

AF:

0.000210

GnomAD4 exome

AF:

0.000175

AC:

247

AN:

1415074

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

113

AN XY:

701096

show subpopulations

Gnomad4 AFR exome

AF:

0.000279

Gnomad4 AMR exome

AF:

0.00104

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:

0.000135

Gnomad4 OTH exome

AF:

0.000685

GnomAD4 genome

AF:

0.000355

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000435

Hom.:

Bravo

AF:

0.000552

ExAC

AF:

0.000173

AC:

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

Nov 24, 2024

The c.849G>T (p.L283F) alteration is located in exon 1 (coding exon 1) of the OR5M3 gene. This alteration results from a G to T substitution at nucleotide position 849, causing the leucine (L) at amino acid position 283 to be replaced by a phenylalanine (F). 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0098

T;T

Eigen

Benign

0.015

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-3.7

.;D

REVEL

Benign

0.13

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.010

.;D

Polyphen

1.0

D;D

Vest4

0.39

MutPred

0.70

Loss of catalytic residue at L283 (P = 0.002);Loss of catalytic residue at L283 (P = 0.002);

MVP

0.52

MPC

0.15

ClinPred

0.090

GERP RS

2.7

Varity_R

0.61

gMVP

0.068

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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