1-248473609-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005495.1(OR2T3):​c.259C>T​(p.Leu87Phe) 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 1,455,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 26)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OR2T3
NM_001005495.1 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.678
Variant links:
Genes affected
OR2T3 (HGNC:14727): (olfactory receptor family 2 subfamily T 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14723247).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR2T3NM_001005495.1 linkc.259C>T p.Leu87Phe missense_variant Exon 1 of 1 ENST00000359594.3 NP_001005495.1 Q8NH03A0A126GVW5
LOC105373279XR_007067006.1 linkn.136-3450G>A intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR2T3ENST00000359594.3 linkc.259C>T p.Leu87Phe missense_variant Exon 1 of 1 6 NM_001005495.1 ENSP00000352604.2 Q8NH03

Frequencies

GnomAD3 genomes
Cov.:
26
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1455524
Hom.:
0
Cov.:
32
AF XY:
0.00000276
AC XY:
2
AN XY:
724296
show subpopulations
Gnomad4 AFR exome
AF:
0.0000610
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:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
26

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.259C>T (p.L87F) alteration is located in exon 1 (coding exon 1) of the OR2T3 gene. This alteration results from a C to T substitution at nucleotide position 259, causing the leucine (L) at amino acid position 87 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
0.33
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0059
T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.019
N
M_CAP
Benign
0.00082
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.077
Sift
Uncertain
0.025
D
Sift4G
Benign
0.10
T
Polyphen
0.35
B
Vest4
0.27
MutPred
0.55
Gain of methylation at K85 (P = 0.0963);
MVP
0.29
ClinPred
0.84
D
GERP RS
1.6
Varity_R
0.16
gMVP
0.038

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-248636910; API