chr17-3278415-G-A

Variant names:

• chr17-3278415-G-A
• rs199722746
• ENST00000573901.3:c.503C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000573901.3(OR3A2):​c.503C>T​(p.Thr168Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000836 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: OR3A2 ENST00000573901.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0120
• Publications: 1 publications found

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]

ACMG classification

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=0.23408204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR3A2	NM_002551.5	c.503C>T	p.Thr168Met	missense_variant	Exon 5 of 5		NP_002542.4
OR3A2	XM_047436157.1	c.527C>T	p.Thr176Met	missense_variant	Exon 7 of 7		XP_047292113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR3A2	ENST00000573901.3	c.503C>T	p.Thr168Met	missense_variant	Exon 5 of 5	3		ENSP00000516654.1
OR3A2	ENST00000641164.1	c.503C>T	p.Thr168Met	missense_variant	Exon 1 of 1			ENSP00000493039.1
OR3A2	ENST00000642052.1	c.503C>T	p.Thr168Met	missense_variant	Exon 2 of 2			ENSP00000493441.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152206 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000596 AC: 15 AN: 251478 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000882 AC: 129 AN: 1461880 Hom.: 0 Cov.: 33 AF XY: 0.0000770 AC XY: 56 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000104 AC: 116 AN: 1112010

Other (OTH) AF: 0.000132 AC: 8 AN: 60392

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152206 Hom.: 0 Cov.: 28 AF XY: 0.0000403 AC XY: 3 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.521C>T (p.T174M) 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 521, causing the threonine (T) at amino acid position 174 to be replaced by a methionine (M). 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	0.086
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.0089	.;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.18	.;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.2	.;.;L
PhyloP100		0.012
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	.;.;N
REVEL	Benign	0.11
Sift	Benign	0.18	.;.;T
Sift4G	Uncertain	0.020	.;.;D
Polyphen		0.77	.;.;P
Vest4		0.26
MutPred		0.47		.;.;Loss of catalytic residue at T174 (P = 0.0169);
MVP		0.37
MPC		0.87
ClinPred		0.058	T
GERP RS		3.9
Varity_R		0.087
gMVP		0.15
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs199722746; hg19: chr17-3181709;