1-248061438-C-A

Variant summary

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

The NM_001004687.2(OR2L3):​c.757C>A​(p.Pro253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,614,052 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.000092 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

OR2L3
NM_001004687.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.29
Variant links:
Genes affected
OR2L3 (HGNC:15009): (olfactory receptor family 2 subfamily L 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]
OR2L13 (HGNC:19578): (olfactory receptor family 2 subfamily L member 13) 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=0.017534703).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2L3NM_001004687.2 linkuse as main transcriptc.757C>A p.Pro253Thr missense_variant 2/2 ENST00000359959.4 NP_001004687.1 Q8NG85

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR2L3ENST00000359959.4 linkuse as main transcriptc.757C>A p.Pro253Thr missense_variant 2/26 NM_001004687.2 ENSP00000353044.3 Q8NG85
OR2L3ENST00000641161.1 linkuse as main transcriptc.757C>A p.Pro253Thr missense_variant 2/2 ENSP00000493424.1 Q8NG85
OR2L3ENST00000641649.1 linkuse as main transcriptc.757C>A p.Pro253Thr missense_variant 3/3 ENSP00000493020.1 Q8NG85

Frequencies

GnomAD3 genomes
AF:
0.0000921
AC:
14
AN:
152072
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00187
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000255
AC:
64
AN:
251400
Hom.:
0
AF XY:
0.000353
AC XY:
48
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.000298
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00127
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000967
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000124
AC:
181
AN:
1461862
Hom.:
1
Cov.:
37
AF XY:
0.000172
AC XY:
125
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.000268
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152190
Hom.:
0
Cov.:
31
AF XY:
0.000134
AC XY:
10
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000113
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000272
AC:
33
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 GeneticsSep 02, 2024The c.757C>A (p.P253T) alteration is located in exon 1 (coding exon 1) of the OR2L3 gene. This alteration results from a C to A substitution at nucleotide position 757, causing the proline (P) 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
0.23
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
6.2
DANN
Benign
0.51
DEOGEN2
Benign
0.018
T;T;T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.0083
N
LIST_S2
Benign
0.81
.;.;T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.018
T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
0.55
N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Pathogenic
-4.7
D;.;.
REVEL
Benign
0.059
Sift
Benign
0.24
T;.;.
Sift4G
Benign
0.33
T;.;.
Polyphen
1.0
D;D;D
Vest4
0.11
MVP
0.40
MPC
0.26
ClinPred
0.13
T
GERP RS
0.85
Varity_R
0.12
gMVP
0.14

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: rs368310262; hg19: chr1-248224740; COSMIC: COSV100742077; API