chr14-21570227-T-C

Variant summary

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

The NM_001005465.2(OR10G3):ā€‹c.518A>Gā€‹(p.Asn173Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,030 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‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000015 ( 0 hom. )

Consequence

OR10G3
NM_001005465.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10
Variant links:
Genes affected
OR10G3 (HGNC:8171): (olfactory receptor family 10 subfamily G member 3) 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=0.15039355).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR10G3NM_001005465.2 linkuse as main transcriptc.518A>G p.Asn173Ser missense_variant 2/2 ENST00000641040.1 NP_001005465.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR10G3ENST00000641040.1 linkuse as main transcriptc.518A>G p.Asn173Ser missense_variant 2/2 NM_001005465.2 ENSP00000493245 P1
OR10G3ENST00000641185.1 linkuse as main transcriptc.518A>G p.Asn173Ser missense_variant 3/3 ENSP00000492973 P1
OR10G3ENST00000641655.1 linkuse as main transcriptn.292-146A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000119
AC:
3
AN:
251318
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135812
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461868
Hom.:
0
Cov.:
62
AF XY:
0.0000151
AC XY:
11
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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
Alfa
AF:
0.000137
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsSep 22, 2022The c.518A>G (p.N173S) alteration is located in exon 1 (coding exon 1) of the OR10G3 gene. This alteration results from a A to G substitution at nucleotide position 518, causing the asparagine (N) at amino acid position 173 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
0.099
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.012
T;T;T
Eigen
Benign
0.016
Eigen_PC
Benign
0.072
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.58
.;.;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M;M;M
MutationTaster
Benign
0.71
N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-4.0
.;.;D
REVEL
Benign
0.15
Sift
Benign
0.044
.;.;D
Sift4G
Benign
0.065
.;.;T
Polyphen
0.20
B;B;B
Vest4
0.20
MVP
0.42
MPC
0.067
ClinPred
0.52
D
GERP RS
3.4
Varity_R
0.35
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: rs767102533; hg19: chr14-22038358; API