1-248638376-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001827.2(OR2T35):ā€‹c.883A>Gā€‹(p.Lys295Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00049 ( 0 hom., cov: 16)
Exomes š‘“: 0.000068 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OR2T35
NM_001001827.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23
Variant links:
Genes affected
OR2T35 (HGNC:31257): (olfactory receptor family 2 subfamily T member 35) 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.

BP4
Computational evidence support a benign effect (MetaRNN=0.09043217).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2T35NM_001001827.2 linkc.883A>G p.Lys295Glu missense_variant 2/2 ENST00000641268.1 NP_001001827.1 Q8NGX2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR2T35ENST00000641268.1 linkc.883A>G p.Lys295Glu missense_variant 2/2 NM_001001827.2 ENSP00000492995.1 Q8NGX2

Frequencies

GnomAD3 genomes
AF:
0.000470
AC:
60
AN:
127594
Hom.:
0
Cov.:
16
show subpopulations
Gnomad AFR
AF:
0.00175
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000777
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00357
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000676
AC:
62
AN:
917170
Hom.:
0
Cov.:
13
AF XY:
0.0000671
AC XY:
32
AN XY:
477158
show subpopulations
Gnomad4 AFR exome
AF:
0.00158
Gnomad4 AMR exome
AF:
0.000139
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000129
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000164
Gnomad4 OTH exome
AF:
0.000230
GnomAD4 genome
AF:
0.000485
AC:
62
AN:
127718
Hom.:
0
Cov.:
16
AF XY:
0.000392
AC XY:
24
AN XY:
61276
show subpopulations
Gnomad4 AFR
AF:
0.00181
Gnomad4 AMR
AF:
0.0000776
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000253
Hom.:
0
ExAC
AF:
0.0000402
AC:
4

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 GeneticsJun 11, 2021The c.883A>G (p.K295E) alteration is located in exon 1 (coding exon 1) of the OR2T35 gene. This alteration results from a A to G substitution at nucleotide position 883, causing the lysine (K) at amino acid position 295 to be replaced by a glutamic acid (E). 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
0.16
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
21
DANN
Benign
0.93
DEOGEN2
Benign
0.026
T;T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.25
.;T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.090
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;L
PrimateAI
Benign
0.21
T
PROVEAN
Uncertain
-3.1
.;D
REVEL
Benign
0.057
Sift
Uncertain
0.0080
.;D
Sift4G
Uncertain
0.0020
.;D
Polyphen
0.77
P;P
Vest4
0.26
MVP
0.50
MPC
2.1
ClinPred
0.22
T
GERP RS
2.8
Varity_R
0.41
gMVP
0.086

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: rs199851170; hg19: chr1-248801677; API