chr17-3292059-T-C

Position:

• chr17-3292059-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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 criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.860

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 Benign. Variant got -14 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]. Clinvar id is 777092.Status of the report is criteria_provided_single_submitter, 1 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR3A1	NM_002550.3	c.524A>G	p.Asn175Ser	missense_variant	2/2	ENST00000323404.2
OR3A2	NM_002551.5	c.-278-7508A>G		intron_variant		ENST00000573901.3
OR3A2	XM_047436157.1	c.-255+7047A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR3A1	ENST00000323404.2	c.524A>G	p.Asn175Ser	missense_variant	2/2		NM_002550.3	P1
OR3A2	ENST00000573901.3	c.-278-7508A>G		intron_variant		3	NM_002551.5	P1
OR3A2	ENST00000573491.5	c.-84-12906A>G		intron_variant		3
OR3A2	ENST00000576166.2	c.-84-12906A>G		intron_variant		5

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

GnomAD3 exomes AF: 0.00239 AC: 600 AN: 251486 Hom.: 2 AF XY: 0.00194 AC XY: 263 AN XY: 135916

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 SAS exome AF: 0.000490

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

Gnomad4 AFR exome AF: 0.0190

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.000689

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.000495

Gnomad4 OTH exome AF: 0.00353

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

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.00556

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.00569

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

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;T
MetaRNN	Benign	0.0046	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-4.2	D;.
REVEL	Benign	0.12
Sift	Benign	0.096	T;.
Sift4G	Benign	0.076	T;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

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

LitVar

Other links and lift over

dbSNP: rs61734043; hg19: chr17-3195353;