Variant 11-56469897-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004742.3(OR5M3):c.601G>A(p.Ala201Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,612,850 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00071 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 9 hom. )

Consequence

OR5M3
NM_001004742.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.778

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03114295).

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5M3	NM_001004742.3 linkuse as main transcript	c.601G>A	p.Ala201Thr	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.601G>A	p.Ala201Thr	missense_variant	2/2	NM_001004742.3	ENSP00000493070.1	Q8NGP4
ENSG00000284732	ENST00000641310.1 linkuse as main transcript	c.144+457G>A		intron_variant			ENSP00000493052.1	A0A286YEX6
ENSG00000284732	ENST00000641599.1 linkuse as main transcript	c.144+457G>A		intron_variant			ENSP00000493241.1	A0A286YF13

Frequencies

GnomAD3 genomes

AF:

0.000710

AC:

108

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000792

AC:

199

AN:

251146

Hom.:

AF XY:

0.000788

AC XY:

107

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00161

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00123

AC:

1797

AN:

1460782

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

867

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00155

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000710

AC:

108

AN:

152068

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.000959

Alfa

AF:

0.000622

Hom.:

Bravo

AF:

0.000759

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000848

AC:

103

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

Jun 13, 2024

The c.601G>A (p.A201T) alteration is located in exon 1 (coding exon 1) of the OR5M3 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the alanine (A) at amino acid position 201 to be replaced by a threonine (T). 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

0.37

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.46

.;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.8

.;D

REVEL

Benign

0.061

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.016

.;D

Polyphen

0.80

P;P

Vest4

0.086

MVP

0.52

MPC

0.23

ClinPred

0.13

GERP RS

3.0

Varity_R

0.45

gMVP

0.077

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