chr17-3420745-G-A

Position:

• chr17-3420745-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012373.3(OR3A3):​c.160G>A​(p.Val54Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR3A3 NM_012373.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.86

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.084439635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR3A3	NM_012373.3	c.160G>A	p.Val54Met	missense_variant	3/3	ENST00000641141.1
OR3A3	NM_001386098.1	c.160G>A	p.Val54Met	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR3A3	ENST00000641141.1	c.160G>A	p.Val54Met	missense_variant	3/3		NM_012373.3	P1
OR3A3	ENST00000574571.4	c.160G>A	p.Val54Met	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.99e-7 AC: 1 AN: 1250812 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 617474

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: 0.00000105

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 18

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

Apr 12, 2022

The c.178G>A (p.V60M) alteration is located in exon 1 (coding exon 1) of the OR3A3 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the valine (V) at amino acid position 60 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	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.0
DANN	Benign	0.76
DEOGEN2	Benign	0.017	.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.30	.;T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.084	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.48	.;.;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.86	.;.;N
REVEL	Benign	0.036
Sift	Benign	0.26	.;.;T
Sift4G	Benign	0.34	.;.;T
Polyphen		0.10	.;.;B
Vest4		0.13
MutPred		0.27		.;.;Gain of sheet (P = 0.0827);
MVP		0.20
MPC		1.1
ClinPred		0.068	T
GERP RS		0.55
Varity_R		0.089
gMVP		0.062

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-3324039;