Variant 17-3420837-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012373.3(OR3A3):c.252G>A(p.Met84Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 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: 𝑓 0.000096 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000020 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR3A3
NM_012373.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.860

Variant links:

Genes affected

OR3A3 (HGNC:8284): (olfactory receptor family 3 subfamily A 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]

OR3A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05803576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR3A3	NM_001386098.1 link	c.252G>A	p.Met84Ile	missense_variant	2/2		NP_001373027.1
OR3A3	NM_012373.3 link	c.252G>A	p.Met84Ile	missense_variant	3/3		NP_036505.3	P47888A0A126GWB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR3A3	ENST00000641141.1 link	c.252G>A	p.Met84Ile	missense_variant	3/3			ENSP00000493061.1		A0A126GWB3
OR3A3	ENST00000574571.4 link	c.252G>A	p.Met84Ile	missense_variant	1/1	6		ENSP00000493211.1		A0A126GWB3

Frequencies

GnomAD3 genomes

AF:

0.0000963

AC:

AN:

145444

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000360

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

149258

Hom.:

AF XY:

0.00

AC XY:

AN XY:

79522

show subpopulations

Gnomad AFR exome

AF:

0.000246

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:

0.0000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1257346

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

628514

show subpopulations

Gnomad4 AFR exome

AF:

0.000310

Gnomad4 AMR exome

AF:

0.0000264

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:

0.0000106

Gnomad4 OTH exome

AF:

0.0000753

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000962

AC:

AN:

145560

Hom.:

Cov.:

AF XY:

0.0000992

AC XY:

AN XY:

70544

show subpopulations

Gnomad4 AFR

AF:

0.000359

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000178

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

Sep 03, 2024

The c.270G>A (p.M90I) alteration is located in exon 1 (coding exon 1) of the OR3A3 gene. This alteration results from a G to A substitution at nucleotide position 270, causing the methionine (M) at amino acid position 90 to be replaced by an isoleucine (I). 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

0.47

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0085

.;.;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.66

.;T;T

M_CAP

Benign

0.00065

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.88

.;.;L

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.7

.;.;D

REVEL

Benign

0.032

Sift

Uncertain

0.022

.;.;D

Sift4G

Uncertain

0.023

.;.;D

Polyphen

0.0050

.;.;B

Vest4

0.27

MutPred

0.42

.;.;Gain of catalytic residue at L95 (P = 0.0803);

MVP

0.37

MPC

1.3

ClinPred

0.043

GERP RS

1.7

Varity_R

0.29

gMVP

0.26

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