1-248295188-G-A

Variant summary

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

The NM_001004692.2(OR2T12):​c.391C>T​(p.Pro131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

Frequency

Genomes: not found (cov: 27)

Consequence

OR2T12
NM_001004692.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.52
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]

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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=0.06472513).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2T12NM_001004692.2 linkuse as main transcriptc.391C>T p.Pro131Ser 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.391C>T p.Pro131Ser missense_variant 3/3 NM_001004692.2 ENSP00000493000.1 Q8NG77

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
Cov.:
82
GnomAD4 genome
Cov.:
27

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 GeneticsDec 20, 2021The c.391C>T (p.P131S) alteration is located in exon 1 (coding exon 1) of the OR2T12 gene. This alteration results from a C to T substitution at nucleotide position 391, causing the proline (P) at amino acid position 131 to be replaced by a serine (S). 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
0.11
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.86
DANN
Benign
0.79
DEOGEN2
Benign
0.0070
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0066
N
LIST_S2
Benign
0.67
.;T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.065
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.0050
N;N
PrimateAI
Benign
0.26
T
PROVEAN
Uncertain
-4.1
.;D
REVEL
Benign
0.074
Sift
Benign
0.13
.;T
Sift4G
Benign
0.20
.;T
Polyphen
0.17
B;B
Vest4
0.045
MutPred
0.52
Gain of MoRF binding (P = 0.0697);Gain of MoRF binding (P = 0.0697);
MVP
0.15
MPC
0.48
ClinPred
0.077
T
GERP RS
-3.1
Varity_R
0.069
gMVP
0.17

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: chr1-248458490; COSMIC: COSV100527998; API