17-3291898-G-C

Position:

• chr17-3291898-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002550.3(OR3A1):​c.685C>G​(p.Leu229Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: OR3A1 NM_002550.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0850

Genes affected

OR3A1 (HGNC:8282): (olfactory receptor family 3 subfamily A member 1) 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 (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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26468074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR3A1	NM_002550.3	c.685C>G	p.Leu229Val	missense_variant	2/2	ENST00000323404.2	NP_002541.2
OR3A2	NM_002551.5	c.-278-7347C>G		intron_variant		ENST00000573901.3	NP_002542.4
OR3A2	XM_047436157.1	c.-255+7208C>G		intron_variant			XP_047292113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR3A1	ENST00000323404.2	c.685C>G	p.Leu229Val	missense_variant	2/2		NM_002550.3	ENSP00000313803	P1
OR3A2	ENST00000573901.3	c.-278-7347C>G		intron_variant		3	NM_002551.5	ENSP00000516654	P1
OR3A2	ENST00000573491.5	c.-84-12745C>G		intron_variant		3		ENSP00000493118
OR3A2	ENST00000576166.2	c.-84-12745C>G		intron_variant		5		ENSP00000493095

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.685C>G (p.L229V) alteration is located in exon 1 (coding exon 1) of the OR3A1 gene. This alteration results from a C to G substitution at nucleotide position 685, causing the leucine (L) at amino acid position 229 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.11
Sift	Uncertain	0.016	D;.
Sift4G	Uncertain	0.020	D;D
Polyphen		0.85	P;.
Vest4		0.46
MutPred		0.61		Gain of MoRF binding (P = 0.0946);.;
MVP		0.40
MPC		0.062
ClinPred		0.49	T
GERP RS		3.0
Varity_R		0.19
gMVP		0.074

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-3195192;