Variant 17-3420625-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BP4_Strong

The NM_012373.3(OR3A3):c.40G>A(p.Glu14Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 150,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000037 ( 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: 1.41

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity OR3A3_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.038158983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR3A3	NM_012373.3 linkuse as main transcript	c.40G>A	p.Glu14Lys	missense_variant	3/3	ENST00000641141.1
OR3A3	NM_001386098.1 linkuse as main transcript	c.40G>A	p.Glu14Lys	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR3A3	ENST00000641141.1 linkuse as main transcript	c.40G>A	p.Glu14Lys	missense_variant	3/3		NM_012373.3	P1
OR3A3	ENST00000574571.4 linkuse as main transcript	c.40G>A	p.Glu14Lys	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.000285

AC:

AN:

150794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000373

AC:

AN:

1365778

Hom.:

Cov.:

AF XY:

0.0000373

AC XY:

AN XY:

669840

show subpopulations

Gnomad4 AFR exome

AF:

0.00142

Gnomad4 AMR exome

AF:

0.0000344

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:

0.00000187

Gnomad4 OTH exome

AF:

0.000107

GnomAD4 genome

AF:

0.000292

AC:

AN:

150908

Hom.:

Cov.:

AF XY:

0.000339

AC XY:

AN XY:

73664

show subpopulations

Gnomad4 AFR

AF:

0.00105

Gnomad4 AMR

AF:

0.0000662

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:

0.000506

Hom.:

ExAC

AF:

0.000244

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

Jun 07, 2024

The c.58G>A (p.E20K) 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 58, causing the glutamic acid (E) at amino acid position 20 to be replaced by a lysine (K). 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

0.22

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

.;.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.88

.;D;D

M_CAP

Benign

0.0017

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

.;.;M

MutationTaster

Benign

0.86

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.1

.;.;N

REVEL

Benign

0.10

Sift

Benign

0.041

.;.;D

Sift4G

Uncertain

0.033

.;.;D

Polyphen

0.044

.;.;B

Vest4

0.23

MVP

0.39

MPC

2.1

ClinPred

0.069

GERP RS

2.4

Varity_R

0.16

gMVP

0.58

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