Variant 11-7796119-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153444.1(OR5P2):c.824C>T(p.Thr275Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 1,605,406 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00025 ( 4 hom., cov: 31)

Exomes 𝑓: 0.00033 ( 12 hom. )

Consequence

OR5P2
NM_153444.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.54

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:

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=0.022180736).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5P2	NM_153444.1 linkuse as main transcript	c.824C>T	p.Thr275Ile	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.824C>T	p.Thr275Ile	missense_variant	1/1	6	NM_153444.1	ENSP00000331823.2	Q8WZ92
ENSG00000271758	ENST00000527565.1 linkuse as main transcript	n.542+82888C>T		intron_variant		3
ENSG00000254951	ENST00000529488.5 linkuse as main transcript	n.532-41598C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

147814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000530

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000642

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000413

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000537

AC:

134

AN:

249728

Hom.:

AF XY:

0.000548

AC XY:

AN XY:

135062

show subpopulations

Gnomad AFR exome

AF:

0.000261

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00100

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000329

AC:

480

AN:

1457486

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

237

AN XY:

725132

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000362

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.000359

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.000250

AC:

AN:

147920

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

AN XY:

72262

show subpopulations

Gnomad4 AFR

AF:

0.0000528

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000642

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.000413

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000412

Hom.:

ExAC

AF:

0.000845

AC:

102

EpiCase

AF:

0.000437

EpiControl

AF:

0.000297

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 01, 2024

The c.824C>T (p.T275I) alteration is located in exon 1 (coding exon 1) of the OR5P2 gene. This alteration results from a C to T substitution at nucleotide position 824, causing the threonine (T) at amino acid position 275 to be replaced by an isoleucine (I). 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

0.21

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.60

DANN

Benign

0.95

DEOGEN2

Benign

0.0090

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.10

M_CAP

Benign

0.0046

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.18

PROVEAN

Benign

-2.2

REVEL

Benign

0.071

Sift

Benign

0.052

Sift4G

Uncertain

0.048

Polyphen

0.012

Vest4

0.16

MVP

0.26

MPC

0.0060

ClinPred

0.024

GERP RS

-3.4

Varity_R

0.050

gMVP

0.096

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