1-158777625-T-C

Position:

chr1-158777625-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005278.2(OR6N2):c.11A>G(p.Tyr4Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 1,609,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

OR6N2
NM_001005278.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00500

Variant links:

Genes affected

OR6N2 (HGNC:15035): (olfactory receptor family 6 subfamily N 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]

OR6N2 links:

OR6N1 (HGNC:15034): (olfactory receptor family 6 subfamily N 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]

OR6N1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02078569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6N2	NM_001005278.2 linkuse as main transcript	c.11A>G	p.Tyr4Cys	missense_variant	2/2	ENST00000641131.1	NP_001005278.1	Q8NGY6A0A126GV57
OR6N1	XM_017000325.2 linkuse as main transcript	c.-193-5430A>G		intron_variant			XP_016855814.1	Q8NGY5
OR6N1	XM_017000326.2 linkuse as main transcript	c.-194+3976A>G		intron_variant			XP_016855815.1	Q8NGY5
OR6N1	XM_017000327.2 linkuse as main transcript	c.-193-5430A>G		intron_variant			XP_016855816.1	Q8NGY5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6N2	ENST00000641131.1 linkuse as main transcript	c.11A>G	p.Tyr4Cys	missense_variant	2/2		NM_001005278.2	ENSP00000493148.1		Q8NGY6

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000693

AC:

AN:

245206

Hom.:

AF XY:

0.0000599

AC XY:

AN XY:

133528

show subpopulations

Gnomad AFR exome

AF:

0.000987

Gnomad AMR exome

AF:

0.0000584

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1457354

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

724826

show subpopulations

Gnomad4 AFR exome

AF:

0.000539

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000217

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jan 11, 2023

The c.11A>G (p.Y4C) alteration is located in exon 1 (coding exon 1) of the OR6N2 gene. This alteration results from a A to G substitution at nucleotide position 11, causing the tyrosine (Y) at amino acid position 4 to be replaced by a cysteine (C). 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

-0.66

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.1

DANN

Benign

0.89

DEOGEN2

Benign

0.0051

T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.36

.;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.20

.;N

REVEL

Benign

0.078

Sift

Benign

0.047

.;D

Sift4G

Benign

0.082

.;T

Polyphen

0.76

P;P

Vest4

0.052

MVP

0.37

MPC

0.13

ClinPred

0.027

GERP RS

-1.1

Varity_R

0.050

gMVP

0.26

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