17-3292059-T-C

Variant names:

• chr17-3292059-T-C
• rs61734043
• NM_002550.3:c.524A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002550.3(OR3A1):​c.524A>G​(p.Asn175Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,614,084 control chromosomes in the GnomAD database, including 20 homozygotes. 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (10 hom.)
• Consequence: OR3A1 NM_002550.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.860
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045971572).
• BP6: Variant 17-3292059-T-C is Benign according to our data. Variant chr17-3292059-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 777092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00662 (1008/152190) while in subpopulation AFR AF = 0.02 (832/41524). AF 95% confidence interval is 0.0189. There are 10 homozygotes in GnomAd4. There are 468 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002550.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR3A1	NM_002550.3	MANE Select	c.524A>G	p.Asn175Ser	missense	Exon 2 of 2	NP_002541.2	A0A126GVP1
	OR3A2	NM_002551.5	MANE Select	c.-278-7508A>G		intron	N/A	NP_002542.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR3A1	ENST00000323404.2	TSL:6 MANE Select	c.524A>G	p.Asn175Ser	missense	Exon 2 of 2	ENSP00000313803.1	P47881
	OR3A2	ENST00000573901.3	TSL:3 MANE Select	c.-278-7508A>G		intron	N/A	ENSP00000516654.1	A0A286YFF0
	OR3A2	ENST00000869173.1		c.-216-9485A>G		intron	N/A	ENSP00000539232.1

Frequencies

GnomAD3 genomes AF: 0.00657 AC: 999 AN: 152072 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00557

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00239 AC: 600 AN: 251486 AF XY: 0.00194

Gnomad AFR exome AF: 0.0210

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000756

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00114 AC: 1666 AN: 1461894 Hom.: 10 Cov.: 30 AF XY: 0.00105 AC XY: 765 AN XY: 727248

African (AFR) AF: 0.0190 AC: 637 AN: 33480

American (AMR) AF: 0.00385 AC: 172 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86258

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53420

Middle Eastern (MID) AF: 0.00693 AC: 40 AN: 5768

European-Non Finnish (NFE) AF: 0.000495 AC: 551 AN: 1112012

Other (OTH) AF: 0.00353 AC: 213 AN: 60396

GnomAD4 genome AF: 0.00662 AC: 1008 AN: 152190 Hom.: 10 Cov.: 32 AF XY: 0.00629 AC XY: 468 AN XY: 74402

African (AFR) AF: 0.0200 AC: 832 AN: 41524

American (AMR) AF: 0.00556 AC: 85 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3464

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.000926 AC: 63 AN: 68004

Other (OTH) AF: 0.00569 AC: 12 AN: 2110

Alfa AF: 0.00279 Hom.: 1

Bravo AF: 0.00741

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0209 AC: 92

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00267 AC: 324

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.00113

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.86
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.12
Sift	Benign	0.096	T
Sift4G	Benign	0.076	T
Polyphen		0.029	B
Vest4		0.17
MVP		0.33
MPC		0.025
ClinPred		0.021	T
GERP RS		1.6
Varity_R		0.15
gMVP		0.072
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs61734043; hg19: chr17-3195353;