Variant 3-98469842-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004736.4(OR5K1):c.266A>G(p.Asn89Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,613,378 control chromosomes in the GnomAD database, including 4 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N89D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 3 hom. )

Consequence

OR5K1
NM_001004736.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0180

Variant links:

Genes affected

OR5K1 (HGNC:8349): (olfactory receptor family 5 subfamily K 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]

OR5K1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010128528).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR5K1	NM_001004736.4 linkuse as main transcript	c.266A>G	p.Asn89Ser	missense_variant	2/2	ENST00000642057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR5K1	ENST00000642057.1 linkuse as main transcript	c.266A>G	p.Asn89Ser	missense_variant	2/2		NM_001004736.4	P1
OR5K1	ENST00000332650.5 linkuse as main transcript	c.266A>G	p.Asn89Ser	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.00302

AC:

459

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.000195

AC:

AN:

251224

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000237

AC:

347

AN:

1461180

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

153

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.00418

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00320

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00306

AC:

465

AN:

152198

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

199

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0104

Gnomad4 AMR

AF:

0.000917

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000481

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 11, 2022

The c.266A>G (p.N89S) alteration is located in exon 1 (coding exon 1) of the OR5K1 gene. This alteration results from a A to G substitution at nucleotide position 266, causing the asparagine (N) at amino acid position 89 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.6

DANN

Benign

0.34

DEOGEN2

Benign

0.0051

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.10

.;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.45

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.93

.;N

REVEL

Benign

0.018

Sift

Benign

0.73

.;T

Sift4G

Benign

0.64

.;T

Polyphen

0.0020

B;B

Vest4

0.075

MVP

0.27

MPC

0.016

ClinPred

0.0023

GERP RS

1.3

Varity_R

0.034

gMVP

0.019

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over