rs759426555

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001004705.2(OR4D10):​c.365G>A​(p.Arg122Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

OR4D10
NM_001004705.2 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.92

Publications

1 publications found
Variant links:
Genes affected
OR4D10 (HGNC:15173): (olfactory receptor family 4 subfamily D member 10) 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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR4D10NM_001004705.2 linkc.365G>A p.Arg122Gln missense_variant Exon 3 of 3 ENST00000530162.2 NP_001004705.1 Q8NGI6A0A126GVJ1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR4D10ENST00000530162.2 linkc.365G>A p.Arg122Gln missense_variant Exon 3 of 3 6 NM_001004705.2 ENSP00000436424.1 Q8NGI6

Frequencies

GnomAD3 genomes
AF:
0.0000724
AC:
11
AN:
151986
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000242
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000200
AC:
5
AN:
250364
AF XY:
0.00000737
show subpopulations
Gnomad AFR exome
AF:
0.000128
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461882
Hom.:
0
Cov.:
32
AF XY:
0.0000193
AC XY:
14
AN XY:
727242
show subpopulations
African (AFR)
AF:
0.0000597
AC:
2
AN:
33480
American (AMR)
AF:
0.0000224
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000504
AC:
2
AN:
39700
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000180
AC:
20
AN:
1112002
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.462
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152102
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74354
show subpopulations
African (AFR)
AF:
0.000241
AC:
10
AN:
41512
American (AMR)
AF:
0.0000655
AC:
1
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4810
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10576
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67966
Other (OTH)
AF:
0.00
AC:
0
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.516
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000907
ExAC
AF:
0.0000412
AC:
5
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
Jul 14, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.365G>A (p.R122Q) alteration is located in exon 1 (coding exon 1) of the OR4D10 gene. This alteration results from a G to A substitution at nucleotide position 365, causing the arginine (R) at amino acid position 122 to be replaced by a glutamine (Q). 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
0.16
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T
Eigen
Benign
-0.019
Eigen_PC
Benign
-0.10
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.75
T
M_CAP
Uncertain
0.099
D
MetaRNN
Uncertain
0.65
D
MetaSVM
Benign
-0.33
T
MutationAssessor
Pathogenic
3.8
H
PhyloP100
7.9
PrimateAI
Benign
0.24
T
PROVEAN
Uncertain
-3.8
D
REVEL
Uncertain
0.42
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.0090
D
Polyphen
0.47
P
Vest4
0.65
MVP
0.85
MPC
0.028
ClinPred
0.40
T
GERP RS
3.8
Varity_R
0.59
gMVP
0.61
Mutation Taster
=78/22
polymorphism

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

Other links and lift over

dbSNP: rs759426555; hg19: chr11-59245267; COSMIC: COSV105374640; API