1-248294896-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004692.2(OR2T12):ā€‹c.683C>Gā€‹(p.Ser228Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,459,798 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 29)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

OR2T12
NM_001004692.2 missense

Scores

4
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.408
Variant links:
Genes affected
OR2T12 (HGNC:19592): (olfactory receptor family 2 subfamily T member 12) 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2T12NM_001004692.2 linkuse as main transcriptc.683C>G p.Ser228Cys missense_variant 3/3 ENST00000641276.1 NP_001004692.1 Q8NG77

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR2T12ENST00000641276.1 linkuse as main transcriptc.683C>G p.Ser228Cys missense_variant 3/3 NM_001004692.2 ENSP00000493000.1 Q8NG77

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251132
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135720
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1459798
Hom.:
0
Cov.:
105
AF XY:
0.0000110
AC XY:
8
AN XY:
726212
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:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
29
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000378
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 GeneticsJan 31, 2022The c.683C>G (p.S228C) alteration is located in exon 1 (coding exon 1) of the OR2T12 gene. This alteration results from a C to G substitution at nucleotide position 683, causing the serine (S) at amino acid position 228 to be replaced by a cysteine (C). 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
0.20
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
20
DANN
Uncertain
0.97
DEOGEN2
Benign
0.0076
T;T
Eigen
Benign
0.018
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.78
.;T
M_CAP
Benign
0.00069
T
MetaRNN
Uncertain
0.59
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.8
H;H
PrimateAI
Benign
0.25
T
PROVEAN
Pathogenic
-4.6
.;D
REVEL
Benign
0.064
Sift
Pathogenic
0.0
.;D
Sift4G
Pathogenic
0.0
.;D
Polyphen
1.0
D;D
Vest4
0.098
MutPred
0.71
Loss of disorder (P = 0.012);Loss of disorder (P = 0.012);
MVP
0.42
MPC
0.68
ClinPred
0.55
D
GERP RS
1.6
Varity_R
0.49
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs746687390; hg19: chr1-248458198; API