1-248473498-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001005495.1(OR2T3):​c.148C>T​(p.Leu50Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 24)
Exomes 𝑓: 0.0000051 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OR2T3
NM_001005495.1 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.574
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 Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.27543584).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2T3NM_001005495.1 linkuse as main transcriptc.148C>T p.Leu50Phe missense_variant 1/1 ENST00000359594.3 NP_001005495.1 Q8NH03A0A126GVW5
LOC105373279XR_007067006.1 linkuse as main transcriptn.136-3339G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR2T3ENST00000359594.3 linkuse as main transcriptc.148C>T p.Leu50Phe missense_variant 1/16 NM_001005495.1 ENSP00000352604.2 Q8NH03

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
145520
Hom.:
0
Cov.:
24
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000151
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000455
AC:
1
AN:
219856
Hom.:
0
AF XY:
0.00000845
AC XY:
1
AN XY:
118294
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000105
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000510
AC:
7
AN:
1373446
Hom.:
0
Cov.:
26
AF XY:
0.00000729
AC XY:
5
AN XY:
685626
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:
0.00000580
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000687
AC:
1
AN:
145520
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
70510
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000151
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000832
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 GeneticsOct 26, 2022The c.148C>T (p.L50F) 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 148, causing the leucine (L) at amino acid position 50 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
0.31
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.010
T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.019
N
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.13
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.045
D
Polyphen
1.0
D
Vest4
0.18
MutPred
0.50
Gain of helix (P = 0.1736);
MVP
0.39
ClinPred
0.27
T
GERP RS
-5.3
Varity_R
0.26
gMVP
0.093

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: rs762513872; hg19: chr1-248636799; API