Variant chr11-5581831-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001005162.2(OR52B6):c.955A>C(p.Ile319Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

OR52B6
NM_001005162.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

OR52B6 (HGNC:15211): (olfactory receptor family 52 subfamily B member 6) 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]

OR52B6 links:

ENSG00000239920 (HGNC:):

ENSG00000239920 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52B6	NM_001005162.2 linkuse as main transcript	c.955A>C	p.Ile319Leu	missense_variant	1/1	ENST00000345043.2	NP_001005162.2	Q8NGF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR52B6	ENST00000345043.2 linkuse as main transcript	c.955A>C	p.Ile319Leu	missense_variant	1/1	6	NM_001005162.2	ENSP00000341581.2	Q8NGF0
ENSG00000239920	ENST00000380259.7 linkuse as main transcript	n.*739+8994T>G		intron_variant		5		ENSP00000369609.3	A0A2U3TZJ3
ENSG00000239920	ENST00000394793.3 linkuse as main transcript	n.255+9126T>G		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

243738

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132328

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457738

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725154

show subpopulations

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:

9.00e-7

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

Jan 20, 2023

The c.955A>C (p.I319L) alteration is located in exon 1 (coding exon 1) of the OR52B6 gene. This alteration results from a A to C substitution at nucleotide position 955, causing the isoleucine (I) at amino acid position 319 to be replaced by a leucine (L). 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

0.13

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0059

Eigen

Benign

0.16

Eigen_PC

Benign

0.095

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.47

M_CAP

Benign

0.0090

MetaRNN

Pathogenic

0.89

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.8

REVEL

Benign

0.24

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.017

Polyphen

0.98

Vest4

0.53

MutPred

0.76

Loss of MoRF binding (P = 0.1185);

MVP

0.33

MPC

0.17

ClinPred

0.80

GERP RS

4.8

Varity_R

0.43

gMVP

0.12

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

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