11-6846178-A-G

Variant summary

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

The NM_178168.1(OR10A5):ā€‹c.496A>Gā€‹(p.Ser166Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00019 ( 0 hom., cov: 32)
Exomes š‘“: 0.00031 ( 0 hom. )

Consequence

OR10A5
NM_178168.1 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90
Variant links:
Genes affected
OR10A5 (HGNC:15131): (olfactory receptor family 10 subfamily A member 5) 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 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=0.067013115).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR10A5NM_178168.1 linkc.496A>G p.Ser166Gly missense_variant 1/1 ENST00000299454.5 NP_835462.1 Q9H207A0A126GWR0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR10A5ENST00000299454.5 linkc.496A>G p.Ser166Gly missense_variant 1/16 NM_178168.1 ENSP00000299454.4 Q9H207
ENSG00000283415ENST00000637205.2 linkn.670+4576T>C intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
152106
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000107
AC:
27
AN:
251264
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135788
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000203
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000315
AC:
460
AN:
1461884
Hom.:
0
Cov.:
33
AF XY:
0.000325
AC XY:
236
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000395
Gnomad4 OTH exome
AF:
0.000248
GnomAD4 genome
AF:
0.000191
AC:
29
AN:
152224
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000256
Hom.:
0
Bravo
AF:
0.000159
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00130
AC:
5
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

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 04, 2022The c.496A>G (p.S166G) alteration is located in exon 1 (coding exon 1) of the OR10A5 gene. This alteration results from a A to G substitution at nucleotide position 496, causing the serine (S) at amino acid position 166 to be replaced by a glycine (G). 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
-0.52
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.10
T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.067
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-3.5
D
REVEL
Benign
0.14
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.034
D
Polyphen
0.49
P
Vest4
0.14
MVP
0.38
MPC
0.30
ClinPred
0.15
T
GERP RS
3.6
Varity_R
0.70
gMVP
0.18

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: rs147640150; hg19: chr11-6867409; COSMIC: COSV105166153; COSMIC: COSV105166153; API