Variant chr9-122553727-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004457.2(OR1N2):c.516T>G(p.Cys172Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR1N2
NM_001004457.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.577

Variant links:

Genes affected

OR1N2 (HGNC:15111): (olfactory receptor family 1 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]

OR1N2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR1N2	NM_001004457.2 linkuse as main transcript	c.516T>G	p.Cys172Trp	missense_variant	1/1	ENST00000373688.3
OR1L8	XM_017014285.2 linkuse as main transcript	c.*23-7198A>C		intron_variant
OR1J2	XR_007061271.1 linkuse as main transcript	n.1541-26226T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR1N2	ENST00000373688.3 linkuse as main transcript	c.516T>G	p.Cys172Trp	missense_variant	1/1		NM_001004457.2	P1
	ENST00000431442.2 linkuse as main transcript	n.1362+50857T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459484

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726134

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

GnomAD4 genome

Cov.:

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

Aug 14, 2023

The c.558T>G (p.C186W) alteration is located in exon 1 (coding exon 1) of the OR1N2 gene. This alteration results from a T to G substitution at nucleotide position 558, causing the cysteine (C) at amino acid position 186 to be replaced by a tryptophan (W). 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

Uncertain

0.56

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

.;T

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.069

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.0063

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Benign

-0.85

MutationAssessor

Pathogenic

3.9

.;H

MutationTaster

Benign

0.99

PrimateAI

Benign

0.33

REVEL

Benign

0.24

Polyphen

1.0

.;D

MVP

0.64

MPC

0.65

ClinPred

1.0

GERP RS

2.1

Varity_R

0.93

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over