11-56700916-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001005213.2(OR9G1):ā€‹c.529T>Cā€‹(p.Phe177Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,146 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 67)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

OR9G1
NM_001005213.2 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.35
Variant links:
Genes affected
OR9G1 (HGNC:15319): (olfactory receptor family 9 subfamily G member 1) 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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31749368).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR9G1NM_001005213.2 linkuse as main transcriptc.529T>C p.Phe177Leu missense_variant 2/2 ENST00000642097.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR9G1ENST00000642097.1 linkuse as main transcriptc.529T>C p.Phe177Leu missense_variant 2/2 NM_001005213.2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152310
Hom.:
0
Cov.:
67
show subpopulations
Gnomad AFR
AF:
0.000169
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249664
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135106
show subpopulations
Gnomad AFR exome
AF:
0.000246
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461836
Hom.:
0
Cov.:
218
AF XY:
0.00000413
AC XY:
3
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152310
Hom.:
0
Cov.:
67
AF XY:
0.0000403
AC XY:
3
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.000169
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:
0.00
Gnomad4 OTH
AF:
0.00
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
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 GeneticsNov 09, 2023The c.529T>C (p.F177L) alteration is located in exon 1 (coding exon 1) of the OR9G1 gene. This alteration results from a T to C substitution at nucleotide position 529, causing the phenylalanine (F) at amino acid position 177 to be replaced by a leucine (L). 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
Pathogenic
0.63
BayesDel_addAF
Benign
-0.038
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.012
T;T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.70
.;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.32
T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Uncertain
2.5
M;M
MutationTaster
Benign
0.61
D
PrimateAI
Benign
0.36
T
PROVEAN
Pathogenic
-5.6
.;D
REVEL
Benign
0.19
Sift
Uncertain
0.014
.;D
Sift4G
Uncertain
0.011
.;D
Polyphen
1.0
D;D
Vest4
0.27
MutPred
0.43
Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);
MVP
0.36
MPC
0.0058
ClinPred
0.97
D
GERP RS
4.5
Varity_R
0.64
gMVP
0.11

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: rs143337566; hg19: chr11-56468392; API