14-20197949-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001386033.1(OR11G2):​c.512C>T​(p.Ser171Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

OR11G2
NM_001386033.1 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07
Variant links:
Genes affected
OR11G2 (HGNC:15346): (olfactory receptor family 11 subfamily G member 2) 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25325614).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR11G2NM_001386033.1 linkuse as main transcriptc.512C>T p.Ser171Phe missense_variant 2/2 ENST00000641879.2 NP_001372962.1
OR11G2NM_001005503.2 linkuse as main transcriptc.512C>T p.Ser171Phe missense_variant 2/2 NP_001005503.2 Q8NGC1A0A126GWS8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR11G2ENST00000641879.2 linkuse as main transcriptc.512C>T p.Ser171Phe missense_variant 2/2 NM_001386033.1 ENSP00000493427.1 A0A126GWS8
OR11G2ENST00000641682.1 linkuse as main transcriptc.512C>T p.Ser171Phe missense_variant 2/2 ENSP00000493171.1 A0A126GWS8

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152120
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251452
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135902
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:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1461866
Hom.:
0
Cov.:
44
AF XY:
0.0000220
AC XY:
16
AN XY:
727240
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:
0.0000369
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152120
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.00000824
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 GeneticsJul 12, 2023The c.614C>T (p.S205F) alteration is located in exon 1 (coding exon 1) of the OR11G2 gene. This alteration results from a C to T substitution at nucleotide position 614, causing the serine (S) at amino acid position 205 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
0.20
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.014
.;.;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.64
.;T;T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.25
T;T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Uncertain
2.1
.;.;M
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-3.7
.;.;D
REVEL
Benign
0.11
Sift
Pathogenic
0.0
.;.;D
Sift4G
Uncertain
0.0050
.;.;D
Polyphen
0.84
.;.;P
Vest4
0.15
MutPred
0.49
.;.;Gain of catalytic residue at Q203 (P = 0.0016);
MVP
0.57
MPC
0.44
ClinPred
0.72
D
GERP RS
4.9
Varity_R
0.52
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: rs775439549; hg19: chr14-20666108; COSMIC: COSV62133103; API