11-4587042-C-T

Variant summary

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

The NM_001005170.4(OR52I2):​c.152C>T​(p.Thr51Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR52I2
NM_001005170.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.122
Variant links:
Genes affected
OR52I2 (HGNC:15221): (olfactory receptor family 52 subfamily I 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=0.05768791).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR52I2NM_001005170.4 linkc.152C>T p.Thr51Ile missense_variant Exon 1 of 1 NP_001005170.2 Q8NH67A0A126GWK8
OR52I2NM_001405760.1 linkc.152C>T p.Thr51Ile missense_variant Exon 2 of 2 NP_001392689.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR52I2ENST00000641896.1 linkc.152C>T p.Thr51Ile missense_variant Exon 2 of 2 ENSP00000493402.1 A0A126GWK8
OR52I2ENST00000641486.1 linkc.152C>T p.Thr51Ile missense_variant Exon 1 of 1 ENSP00000493314.1 A0A126GWK8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461862
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
727236
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.230C>T (p.T77I) alteration is located in exon 1 (coding exon 1) of the OR52I2 gene. This alteration results from a C to T substitution at nucleotide position 230, causing the threonine (T) at amino acid position 77 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
0.10
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
9.8
DANN
Benign
0.88
DEOGEN2
Benign
0.00041
.;.;T
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.58
.;T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.058
T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-0.12
.;.;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.41
.;.;N
REVEL
Benign
0.021
Sift
Benign
0.21
.;.;T
Sift4G
Benign
0.14
.;.;T
Polyphen
0.074
.;.;B
Vest4
0.059
MVP
0.13
MPC
0.21
ClinPred
0.26
T
GERP RS
1.1
Varity_R
0.047
gMVP
0.098

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: rs1846307514; hg19: chr11-4608272; API