17-3291691-G-T

Variant names:

• chr17-3291691-G-T
• rs760005941
• NM_002550.3:c.892C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002550.3(OR3A1):​c.892C>A​(p.Pro298Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OR3A1 NM_002550.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11868185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR3A1	NM_002550.3	c.892C>A	p.Pro298Thr	missense_variant	Exon 2 of 2	ENST00000323404.2	NP_002541.2
OR3A2	NM_002551.5	c.-278-7140C>A		intron_variant	Intron 2 of 4		NP_002542.4
OR3A2	XM_047436157.1	c.-254-7140C>A		intron_variant	Intron 4 of 6		XP_047292113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR3A1	ENST00000323404.2	c.892C>A	p.Pro298Thr	missense_variant	Exon 2 of 2	6	NM_002550.3	ENSP00000313803.1
OR3A2	ENST00000573901.3	c.-278-7140C>A		intron_variant	Intron 2 of 4	3		ENSP00000516654.1
OR3A2	ENST00000573491.5	c.-84-12538C>A		intron_variant	Intron 3 of 4	3		ENSP00000493118.1
OR3A2	ENST00000576166.2	c.-84-12538C>A		intron_variant	Intron 2 of 3	5		ENSP00000493095.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251328 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135820

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458988 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725076

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.892C>A (p.P298T) alteration is located in exon 1 (coding exon 1) of the OR3A1 gene. This alteration results from a C to A substitution at nucleotide position 892, causing the proline (P) at amino acid position 298 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	Benign	0.080
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.73
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N;.
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.054
Sift	Benign	0.15	T;.
Sift4G	Uncertain	0.056	T;T
Polyphen		0.0010	B;.
Vest4		0.10
MutPred		0.42		Gain of MoRF binding (P = 0.0567);.;
MVP		0.36
MPC		0.025
ClinPred		0.030	T
GERP RS		1.5
Varity_R		0.10
gMVP		0.087

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

LitVar

Other links and lift over

dbSNP: rs760005941; hg19: chr17-3194985; COSMIC: COSV100041666;