Variant 17-3278658-C-T 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_002551.5(OR3A2):c.260G>A(p.Arg87His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000819 in 1,441,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

OR3A2
NM_002551.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.05

Variant links:

Genes affected

OR3A2 (HGNC:8283): (olfactory receptor family 3 subfamily A member 2) 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]

OR3A2 links:

Genome browser will be placed here

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=0.05918306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR3A2	NM_002551.5 linkuse as main transcript	c.260G>A	p.Arg87His	missense_variant	5/5		NP_002542.4	P47893A0A126GVQ3
OR3A2	XM_047436157.1 linkuse as main transcript	c.284G>A	p.Arg95His	missense_variant	7/7		XP_047292113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
OR3A2	ENST00000573901.3 linkuse as main transcript	c.260G>A	p.Arg87His	missense_variant	5/5	3	ENSP00000516654.1	A0A286YFF0
OR3A2	ENST00000641164.1 linkuse as main transcript	c.260G>A	p.Arg87His	missense_variant	1/1		ENSP00000493039.1	A0A286YFF0
OR3A2	ENST00000642052.1 linkuse as main transcript	c.260G>A	p.Arg87His	missense_variant	2/2		ENSP00000493441.1	A0A286YFF0

Frequencies

GnomAD3 genomes

AF:

0.000109

AC:

AN:

146188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000483

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:

0.0000300

Gnomad OTH

AF:

0.000518

GnomAD3 exomes

AF:

0.000178

AC:

AN:

157716

Hom.:

AF XY:

0.000142

AC XY:

AN XY:

84288

show subpopulations

Gnomad AFR exome

AF:

0.000346

Gnomad AMR exome

AF:

0.000530

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000918

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.000464

GnomAD4 exome

AF:

0.0000787

AC:

102

AN:

1295248

Hom.:

Cov.:

AF XY:

0.0000788

AC XY:

AN XY:

647316

show subpopulations

Gnomad4 AFR exome

AF:

0.000134

Gnomad4 AMR exome

AF:

0.000536

Gnomad4 ASJ exome

AF:

0.0000411

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000249

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000647

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000109

AC:

AN:

146188

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

70808

show subpopulations

Gnomad4 AFR

AF:

0.000153

Gnomad4 AMR

AF:

0.000483

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000300

Gnomad4 OTH

AF:

0.000518

Alfa

AF:

0.000144

Hom.:

Bravo

AF:

0.000178

ESP6500AA

AF:

0.000255

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000122

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

Dec 03, 2021

The c.278G>A (p.R93H) alteration is located in exon 1 (coding exon 1) of the OR3A2 gene. This alteration results from a G to A substitution at nucleotide position 278, causing the arginine (R) at amino acid position 93 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

Benign

0.074

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.53

DANN

Benign

0.56

DEOGEN2

Benign

0.0038

.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.17

.;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.059

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.3

.;.;N

PrimateAI

Benign

0.21

PROVEAN

Benign

1.4

.;.;N

REVEL

Benign

0.039

Sift

Benign

0.64

.;.;T

Sift4G

Benign

0.29

.;.;T

Polyphen

0.0050

.;.;B

Vest4

0.018

MVP

0.17

MPC

0.92

ClinPred

0.0046

GERP RS

-2.0

Varity_R

0.025

gMVP

0.17

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