11-7825404-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_153445.2(OR5P3):​c.569C>T​(p.Ser190Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

OR5P3
NM_153445.2 missense

Scores

2
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27
Variant links:
Genes affected
OR5P3 (HGNC:14784): (olfactory receptor family 5 subfamily P member 3) 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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3182277).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR5P3NM_153445.2 linkuse as main transcriptc.569C>T p.Ser190Phe missense_variant 2/2 ENST00000641167.1 NP_703146.1 Q8WZ94A0A126GVE6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR5P3ENST00000641167.1 linkuse as main transcriptc.569C>T p.Ser190Phe missense_variant 2/2 NM_153445.2 ENSP00000492944.1 Q8WZ94
ENSG00000271758ENST00000527565.1 linkuse as main transcriptn.542+53603C>T intron_variant 3
ENSG00000254951ENST00000529488.5 linkuse as main transcriptn.531+53603C>T intron_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461682
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727164
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:
0.00000360
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32

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 22, 2024The c.569C>T (p.S190F) alteration is located in exon 1 (coding exon 1) of the OR5P3 gene. This alteration results from a C to T substitution at nucleotide position 569, causing the serine (S) at amino acid position 190 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
0.20
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.014
T;T
Eigen
Benign
0.083
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.21
N
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.32
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Pathogenic
3.2
M;M
PrimateAI
Benign
0.28
T
PROVEAN
Pathogenic
-5.0
.;D
REVEL
Benign
0.11
Sift
Uncertain
0.0060
.;D
Sift4G
Uncertain
0.0020
.;D
Polyphen
0.92
P;P
Vest4
0.22
MutPred
0.63
Gain of catalytic residue at S190 (P = 0.1161);Gain of catalytic residue at S190 (P = 0.1161);
MVP
0.55
MPC
0.011
ClinPred
0.67
D
GERP RS
3.3
Varity_R
0.21
gMVP
0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748564383; hg19: chr11-7846951; API