Genetic Variant OR3A3:p.Ile95Thr (chr17-3420869-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000641141.1(OR3A3):c.284T>C(p.Ile95Thr) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 0.000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR3A3
ENST00000641141.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.95

Publications

2 publications found

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 was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR3A3	NM_001386098.1 link	c.284T>C	p.Ile95Thr	missense_variant	Exon 2 of 2		NP_001373027.1
OR3A3	NM_012373.3 link	c.284T>C	p.Ile95Thr	missense_variant	Exon 3 of 3		NP_036505.3	P47888A0A126GWB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR3A3	ENST00000641141.1 link	c.284T>C	p.Ile95Thr	missense_variant	Exon 3 of 3			ENSP00000493061.1		A0A126GWB3
OR3A3	ENST00000574571.4 link	c.284T>C	p.Ile95Thr	missense_variant	Exon 1 of 1	6		ENSP00000493211.1		A0A126GWB3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000853

AC:

AN:

187532

AF XY:

0.0000391

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000577

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000178

AC:

AN:

1406562

Hom.:

Cov.:

AF XY:

0.00000999

AC XY:

AN XY:

700760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32168

American (AMR)

AF:

0.000580

AC:

AN:

43114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25378

East Asian (EAS)

AF:

0.00

AC:

AN:

39108

South Asian (SAS)

AF:

0.00

AC:

AN:

84562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5110

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065738

Other (OTH)

AF:

0.00

AC:

AN:

58442

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000342

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 20, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.302T>C (p.I101T) alteration is located in exon 1 (coding exon 1) of the OR3A3 gene. This alteration results from a T to C substitution at nucleotide position 302, causing the isoleucine (I) at amino acid position 101 to be replaced by a threonine (T). 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0086

.;.;T

Eigen

Benign

0.092

Eigen_PC

Benign

-0.087

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;D;D

M_CAP

Benign

0.00067

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.3

.;.;M

PhyloP100

6.9

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-4.1

.;.;D

REVEL

Benign

0.21

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0010

.;.;D

Polyphen

0.77

.;.;P

Vest4

0.57

MutPred

0.71

.;.;Gain of disorder (P = 0.0062);

MVP

0.76

MPC

2.2

ClinPred

0.75

GERP RS

2.7

PromoterAI

0.046

Neutral

(source)

Varity_R

0.40

gMVP

0.068

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over