Variant 17-3420959-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012373.3(OR3A3):c.374G>A(p.Arg125Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000232 in 1,612,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 21)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

OR3A3
NM_012373.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR3A3	NM_001386098.1 linkuse as main transcript	c.374G>A	p.Arg125Gln	missense_variant	2/2		NP_001373027.1
OR3A3	NM_012373.3 linkuse as main transcript	c.374G>A	p.Arg125Gln	missense_variant	3/3		NP_036505.3	P47888A0A126GWB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR3A3	ENST00000641141.1 linkuse as main transcript	c.374G>A	p.Arg125Gln	missense_variant	3/3			ENSP00000493061.1		A0A126GWB3
OR3A3	ENST00000574571.4 linkuse as main transcript	c.374G>A	p.Arg125Gln	missense_variant	1/1	6		ENSP00000493211.1		A0A126GWB3

Frequencies

GnomAD3 genomes

AF:

0.0000798

AC:

AN:

150440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000151

AC:

AN:

245030

Hom.:

AF XY:

0.000143

AC XY:

AN XY:

133312

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000291

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:

0.000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000248

AC:

362

AN:

1461572

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

162

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000305

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000798

AC:

AN:

150440

Hom.:

Cov.:

AF XY:

0.0000683

AC XY:

AN XY:

73218

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000151

ExAC

AF:

0.000140

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

Apr 29, 2024

The c.392G>A (p.R131Q) 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 392, causing the arginine (R) at amino acid position 131 to be replaced by a glutamine (Q). 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

0.25

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.068

.;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.82

.;T;T

M_CAP

Benign

0.0071

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Uncertain

-0.24

MutationAssessor

Pathogenic

3.3

.;.;M

PrimateAI

Benign

0.16

PROVEAN

Uncertain

-3.6

.;.;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0080

.;.;D

Sift4G

Pathogenic

0.0010

.;.;D

Polyphen

1.0

.;.;D

Vest4

0.14

MVP

0.92

MPC

1.6

ClinPred

0.75

GERP RS

1.5

Varity_R

0.46

gMVP

0.56

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