Variant chr11-7796077-C-T 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_153444.1(OR5P2):c.866G>A(p.Arg289Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000677 in 147,662 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: 𝑓 0.0000068 ( 0 hom., cov: 31)

Consequence

OR5P2
NM_153444.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02

Variant links:

Genes affected

OR5P2 (HGNC:14783): (olfactory receptor family 5 subfamily P 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]

OR5P2 links:

ENSG00000271758 (HGNC:):

ENSG00000271758 links:

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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, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5P2	NM_153444.1 linkuse as main transcript	c.866G>A	p.Arg289Lys	missense_variant	1/1	ENST00000329434.3	NP_703145.1	Q8WZ92A0A126GVJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR5P2	ENST00000329434.3 linkuse as main transcript	c.866G>A	p.Arg289Lys	missense_variant	1/1	6	NM_153444.1	ENSP00000331823.2	Q8WZ92
ENSG00000271758	ENST00000527565.1 linkuse as main transcript	n.542+82930G>A		intron_variant		3
ENSG00000254951	ENST00000529488.5 linkuse as main transcript	n.532-41556G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000677

AC:

AN:

147662

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000677

AC:

AN:

147662

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

72040

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000663

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

Bravo

AF:

0.0000189

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

May 05, 2023

The c.866G>A (p.R289K) alteration is located in exon 1 (coding exon 1) of the OR5P2 gene. This alteration results from a G to A substitution at nucleotide position 866, causing the arginine (R) at amino acid position 289 to be replaced by a lysine (K). 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

0.19

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0090

Eigen

Benign

-0.0056

Eigen_PC

Benign

0.084

FATHMM_MKL

Benign

0.24

M_CAP

Benign

0.0072

MetaRNN

Pathogenic

0.89

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.13

Sift

Benign

0.078

Sift4G

Uncertain

0.040

Polyphen

0.55

Vest4

0.73

MutPred

0.80

Gain of methylation at R289 (P = 0.0122);

MVP

0.66

MPC

0.0093

ClinPred

0.95

GERP RS

5.5

Varity_R

0.41

gMVP

0.23

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