11-7796360-G-A

Variant summary

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

The NM_153444.1(OR5P2):​c.583C>T​(p.Leu195Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,316 control chromosomes in the GnomAD database, including 1 homozygotes. 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: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 1 hom. )

Consequence

OR5P2
NM_153444.1 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.897
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]

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=0.05257982).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR5P2NM_153444.1 linkc.583C>T p.Leu195Phe missense_variant 1/1 ENST00000329434.3 NP_703145.1 Q8WZ92A0A126GVJ7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR5P2ENST00000329434.3 linkc.583C>T p.Leu195Phe missense_variant 1/16 NM_153444.1 ENSP00000331823.2 Q8WZ92
ENSG00000271758ENST00000527565.1 linkn.542+82647C>T intron_variant 3
ENSG00000254951ENST00000529488.5 linkn.532-41839C>T intron_variant 5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1457316
Hom.:
1
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
725056
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1

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 submitterclinical testingAmbry GeneticsApr 15, 2024The c.583C>T (p.L195F) 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 583, causing the leucine (L) at amino acid position 195 to be replaced by a phenylalanine (F). 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
-0.40
T
BayesDel_noAF
Benign
-0.81
CADD
Benign
14
DANN
Benign
0.57
DEOGEN2
Benign
0.0040
T
Eigen
Benign
-0.99
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.050
N
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.053
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.9
L
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.017
Sift
Benign
0.54
T
Sift4G
Benign
0.20
T
Polyphen
0.050
B
Vest4
0.058
MutPred
0.50
Gain of catalytic residue at L195 (P = 0.0791);
MVP
0.12
MPC
0.0058
ClinPred
0.075
T
GERP RS
0.36
Varity_R
0.045
gMVP
0.091

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.

Other links and lift over

dbSNP: rs769876662; hg19: chr11-7817907; COSMIC: COSV104628989; API