Genetic Variant OR3A2:p.Ala150Glu (chr17-3278469-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000573901.3(OR3A2):c.449C>A(p.Ala150Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A150V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR3A2
ENST00000573901.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17820889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR3A2	NM_002551.5 link	c.449C>A	p.Ala150Glu	missense_variant	Exon 5 of 5		NP_002542.4	P47893A0A126GVQ3
OR3A2	XM_047436157.1 link	c.473C>A	p.Ala158Glu	missense_variant	Exon 7 of 7		XP_047292113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
OR3A2	ENST00000573901.3 link	c.449C>A	p.Ala150Glu	missense_variant	Exon 5 of 5	3	ENSP00000516654.1	A0A286YFF0
OR3A2	ENST00000641164.1 link	c.449C>A	p.Ala150Glu	missense_variant	Exon 1 of 1		ENSP00000493039.1	A0A286YFF0
OR3A2	ENST00000642052.1 link	c.449C>A	p.Ala150Glu	missense_variant	Exon 2 of 2		ENSP00000493441.1	A0A286YFF0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.3

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.14

.;.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.3

.;.;M

PhyloP100

-1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-2.3

.;.;N

REVEL

Benign

0.20

Sift

Benign

0.23

.;.;T

Sift4G

Benign

0.25

.;.;T

Polyphen

0.35

.;.;B

Vest4

0.31

MutPred

0.62

.;.;Loss of MoRF binding (P = 0.0865);

MVP

0.62

MPC

1.2

ClinPred

0.30

GERP RS

-1.2

Varity_R

0.27

gMVP

0.23

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over