Variant 11-56470137-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001004742.3(OR5M3):c.361T>C(p.Tyr121His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR5M3
NM_001004742.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.18

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5M3	NM_001004742.3 link	c.361T>C	p.Tyr121His	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.361T>C	p.Tyr121His	missense_variant	2/2	NM_001004742.3	ENSP00000493070.1	Q8NGP4
ENSG00000284732	ENST00000641310.1 link	c.144+217T>C		intron_variant			ENSP00000493052.1	A0A286YEX6
ENSG00000284732	ENST00000641599.1 link	c.144+217T>C		intron_variant			ENSP00000493241.1	A0A286YF13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249458

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134972

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:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000206

AC:

AN:

1452864

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723170

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:

9.06e-7

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Mar 18, 2024

The c.361T>C (p.Y121H) alteration is located in exon 1 (coding exon 1) of the OR5M3 gene. This alteration results from a T to C substitution at nucleotide position 361, causing the tyrosine (Y) at amino acid position 121 to be replaced by a histidine (H). 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

0.35

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

T;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

.;D

M_CAP

Benign

0.0044

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.4

M;M

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-4.8

.;D

REVEL

Benign

0.23

Sift

Uncertain

0.021

.;D

Sift4G

Benign

0.087

.;T

Polyphen

0.99

D;D

Vest4

0.18

MutPred

0.68

Gain of catalytic residue at Y121 (P = 0.0514);Gain of catalytic residue at Y121 (P = 0.0514);

MVP

0.57

MPC

0.072

ClinPred

0.63

GERP RS

5.1

Varity_R

0.41

gMVP

0.34

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