1-158717962-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005327.3(OR6K3):c.154G>A(p.Asp52Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,613,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D52Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

OR6K3
NM_001005327.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00900

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0782848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR6K3	NM_001005327.3 link	c.154G>A	p.Asp52Asn	missense_variant	Exon 2 of 2	ENST00000368145.2	NP_001005327.2	Q8NGY3A0A0C4DFU5
OR6K3	XM_047420296.1 link	c.154G>A	p.Asp52Asn	missense_variant	Exon 3 of 3		XP_047276252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR6K3	ENST00000368145.2 link	c.154G>A	p.Asp52Asn	missense_variant	Exon 2 of 2	6	NM_001005327.3	ENSP00000357127.1		A0A0C4DFU5
OR6K3	ENST00000368146.1 link	c.202G>A	p.Asp68Asn	missense_variant	Exon 1 of 1	6		ENSP00000357128.1		Q8NGY3

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000958

AC:

AN:

250560

AF XY:

0.0000811

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000135

AC:

197

AN:

1461382

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

727032

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33454

American (AMR)

AF:

0.0000224

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000167

AC:

186

AN:

1111612

Other (OTH)

AF:

0.0000828

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000593

AC:

AN:

151758

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74112

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41314

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67918

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.154G>A (p.D52N) alteration is located in exon 1 (coding exon 1) of the OR6K3 gene. This alteration results from a G to A substitution at nucleotide position 154, causing the aspartic acid (D) at amino acid position 52 to be replaced by an asparagine (N). 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

0.17

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.010

.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

.;L

PhyloP100

-0.0090

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-2.6

D;N

REVEL

Benign

0.016

Sift

Benign

0.11

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.13

.;B

Vest4

0.11

MVP

0.15

MPC

0.039

ClinPred

0.033

GERP RS

2.2

PromoterAI

0.0016

Neutral

(source)

Varity_R

0.049

gMVP

0.082

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-158717962-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over