Variant chr17-3420739-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_012373.3(OR3A3):c.154G>A(p.Val52Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 18)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

OR3A3
NM_012373.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.391

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00775519).

BP6

Variant 17-3420739-G-A is Benign according to our data. Variant chr17-3420739-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3205372.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR3A3	NM_012373.3 linkuse as main transcript	c.154G>A	p.Val52Ile	missense_variant	3/3	ENST00000641141.1
OR3A3	NM_001386098.1 linkuse as main transcript	c.154G>A	p.Val52Ile	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR3A3	ENST00000641141.1 linkuse as main transcript	c.154G>A	p.Val52Ile	missense_variant	3/3		NM_012373.3	P1
OR3A3	ENST00000574571.4 linkuse as main transcript	c.154G>A	p.Val52Ile	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.000467

AC:

AN:

143616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000417

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000212

Gnomad ASJ

AF:

0.00296

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.000262

Gnomad FIN

AF:

0.000204

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000438

AC:

AN:

139396

Hom.:

AF XY:

0.000533

AC XY:

AN XY:

73142

show subpopulations

Gnomad AFR exome

AF:

0.000640

Gnomad AMR exome

AF:

0.000335

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.0000772

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000136

Gnomad NFE exome

AF:

0.000636

Gnomad OTH exome

AF:

0.000856

GnomAD4 exome

AF:

0.000455

AC:

578

AN:

1270942

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

286

AN XY:

627094

show subpopulations

Gnomad4 AFR exome

AF:

0.000241

Gnomad4 AMR exome

AF:

0.000422

Gnomad4 ASJ exome

AF:

0.00219

Gnomad4 EAS exome

AF:

0.0000540

Gnomad4 SAS exome

AF:

0.0000283

Gnomad4 FIN exome

AF:

0.000427

Gnomad4 NFE exome

AF:

0.000476

Gnomad4 OTH exome

AF:

0.000376

GnomAD4 genome

AF:

0.000466

AC:

AN:

143734

Hom.:

Cov.:

AF XY:

0.000504

AC XY:

AN XY:

69480

show subpopulations

Gnomad4 AFR

AF:

0.000416

Gnomad4 AMR

AF:

0.000211

Gnomad4 ASJ

AF:

0.00296

Gnomad4 EAS

AF:

0.000199

Gnomad4 SAS

AF:

0.000262

Gnomad4 FIN

AF:

0.000204

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000716

Hom.:

Bravo

AF:

0.000484

ESP6500AA

AF:

0.000275

AC:

ESP6500EA

AF:

0.000261

AC:

ExAC

AF:

0.000400

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.17

DANN

Benign

0.15

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0046

M_CAP

Benign

0.00093

MetaRNN

Benign

0.0078

T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

Polyphen

0.0

.;.;B

Vest4

0.028

MVP

0.13

MPC

0.92

ClinPred

0.00043

GERP RS

-2.4

Varity_R

0.020

gMVP

0.050

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