Variant 17-3278050-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002551.5(OR3A2):c.868C>T(p.Pro290Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OR3A2
NM_002551.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.57

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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR3A2	NM_002551.5 linkuse as main transcript	c.868C>T	p.Pro290Ser	missense_variant	5/5		NP_002542.4	P47893A0A126GVQ3
OR3A2	XM_047436157.1 linkuse as main transcript	c.892C>T	p.Pro298Ser	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.868C>T	p.Pro290Ser	missense_variant	5/5	3	ENSP00000516654.1	A0A286YFF0
OR3A2	ENST00000641164.1 linkuse as main transcript	c.868C>T	p.Pro290Ser	missense_variant	1/1		ENSP00000493039.1	A0A286YFF0
OR3A2	ENST00000642052.1 linkuse as main transcript	c.868C>T	p.Pro290Ser	missense_variant	2/2		ENSP00000493441.1	A0A286YFF0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250128

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726500

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 04, 2022

The c.886C>T (p.P296S) alteration is located in exon 1 (coding exon 1) of the OR3A2 gene. This alteration results from a C to T substitution at nucleotide position 886, causing the proline (P) at amino acid position 296 to be replaced by a serine (S). 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

Uncertain

0.35

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;.;T

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.77

.;T;T

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.91

D;D;D

MetaSVM

Uncertain

0.26

MutationAssessor

Pathogenic

3.4

.;.;M

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-6.6

.;.;D

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

.;.;D

Sift4G

Uncertain

0.0020

.;.;D

Polyphen

1.0

.;.;D

Vest4

0.80

MutPred

0.73

.;.;Loss of loop (P = 0.2237);

MVP

0.72

MPC

1.8

ClinPred

1.0

GERP RS

4.9

Varity_R

0.91

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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