Variant rs857703 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001005327.3(OR6K3):c.682C>T(p.Pro228Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,613,112 control chromosomes in the GnomAD database, including 112,162 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.32 ( 8911 hom., cov: 31)

Exomes 𝑓: 0.37 ( 103251 hom. )

Consequence

OR6K3
NM_001005327.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.796

Variant links:

Genes affected

OR6K3 (HGNC:15030): (olfactory receptor family 6 subfamily K 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]

OR6K3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.8157234E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6K3	NM_001005327.3 linkuse as main transcript	c.682C>T	p.Pro228Ser	missense_variant	2/2	ENST00000368145.2	NP_001005327.2	Q8NGY3A0A0C4DFU5
OR6K3	XM_047420296.1 linkuse as main transcript	c.682C>T	p.Pro228Ser	missense_variant	3/3		XP_047276252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6K3	ENST00000368145.2 linkuse as main transcript	c.682C>T	p.Pro228Ser	missense_variant	2/2	6	NM_001005327.3	ENSP00000357127.1		A0A0C4DFU5
OR6K3	ENST00000368146.1 linkuse as main transcript	c.730C>T	p.Pro244Ser	missense_variant	1/1	6		ENSP00000357128.1		Q8NGY3

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47974

AN:

151822

Hom.:

8912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.336

GnomAD3 exomes

AF:

0.362

AC:

90603

AN:

250278

Hom.:

17588

AF XY:

0.359

AC XY:

48555

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.436

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.474

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.382

GnomAD4 exome

AF:

0.370

AC:

541214

AN:

1461172

Hom.:

103251

Cov.:

AF XY:

0.366

AC XY:

266281

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.399

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.402

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.384

Gnomad4 OTH exome

AF:

0.362

GnomAD4 genome

AF:

0.316

AC:

47978

AN:

151940

Hom.:

8911

Cov.:

AF XY:

0.321

AC XY:

23825

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.374

Gnomad4 ASJ

AF:

0.339

Gnomad4 EAS

AF:

0.440

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.482

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.339

Alfa

AF:

0.372

Hom.:

27713

Bravo

AF:

0.307

TwinsUK

AF:

0.371

AC:

1374

ALSPAC

AF:

0.382

AC:

1472

ESP6500AA

AF:

0.134

AC:

589

ESP6500EA

AF:

0.378

AC:

3247

ExAC

AF:

0.356

AC:

43215

Asia WGS

AF:

0.317

AC:

1099

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0099

.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.098

T;T

MetaRNN

Benign

0.00028

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.028

Sift

Benign

0.10

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.080

.;B

Vest4

0.078

MPC

0.055

ClinPred

0.0052

GERP RS

0.81

Varity_R

0.082

gMVP

0.075

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over