11-58402652-A-G

Variant summary

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

The NM_001005469.2(OR5B3):ā€‹c.758T>Cā€‹(p.Ile253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,714 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. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000096 ( 0 hom. )

Consequence

OR5B3
NM_001005469.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.264
Variant links:
Genes affected
OR5B3 (HGNC:8324): (olfactory receptor family 5 subfamily B 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 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=0.040151834).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR5B3NM_001005469.2 linkuse as main transcriptc.758T>C p.Ile253Thr missense_variant 2/2 ENST00000641865.1 NP_001005469.1 Q8NH48A0A126GVH3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR5B3ENST00000641865.1 linkuse as main transcriptc.758T>C p.Ile253Thr missense_variant 2/2 NM_001005469.2 ENSP00000493217.1 Q8NH48

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251252
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461714
Hom.:
0
Cov.:
34
AF XY:
0.0000124
AC XY:
9
AN XY:
727152
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

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 GeneticsAug 02, 2023The c.758T>C (p.I253T) alteration is located in exon 1 (coding exon 1) of the OR5B3 gene. This alteration results from a T to C substitution at nucleotide position 758, causing the isoleucine (I) at amino acid position 253 to be replaced by a threonine (T). 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
0.12
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
11
DANN
Benign
0.74
DEOGEN2
Benign
0.013
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.26
.;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.040
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.41
N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-2.2
.;N
REVEL
Benign
0.0090
Sift
Benign
0.15
.;T
Sift4G
Benign
0.22
.;T
Polyphen
0.0050
B;B
Vest4
0.10
MutPred
0.29
Gain of catalytic residue at I253 (P = 0.0589);Gain of catalytic residue at I253 (P = 0.0589);
MVP
0.12
MPC
0.035
ClinPred
0.018
T
GERP RS
0.30
Varity_R
0.12
gMVP
0.035

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: rs746290766; hg19: chr11-58170125; API