rs150042729

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001968.1(OR6S1):​c.625G>A​(p.Val209Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,614,090 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

OR6S1
NM_001001968.1 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0880

Publications

3 publications found
Variant links:
Genes affected
OR6S1 (HGNC:15363): (olfactory receptor family 6 subfamily S 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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1280638).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR6S1NM_001001968.1 linkc.625G>A p.Val209Ile missense_variant Exon 1 of 1 ENST00000320704.3 NP_001001968.1 Q8NH40

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR6S1ENST00000320704.3 linkc.625G>A p.Val209Ile missense_variant Exon 1 of 1 6 NM_001001968.1 ENSP00000313110.3 Q8NH40

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152102
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000796
AC:
20
AN:
251404
AF XY:
0.0000957
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000999
AC:
146
AN:
1461870
Hom.:
1
Cov.:
46
AF XY:
0.000107
AC XY:
78
AN XY:
727234
show subpopulations
African (AFR)
AF:
0.0000597
AC:
2
AN:
33480
American (AMR)
AF:
0.0000894
AC:
4
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.0000383
AC:
1
AN:
26136
East Asian (EAS)
AF:
0.0000756
AC:
3
AN:
39700
South Asian (SAS)
AF:
0.000116
AC:
10
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.000109
AC:
121
AN:
1112002
Other (OTH)
AF:
0.0000828
AC:
5
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
8
16
25
33
41
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<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:
0.000125
AC:
19
AN:
152220
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74414
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41534
American (AMR)
AF:
0.000196
AC:
3
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5178
South Asian (SAS)
AF:
0.000415
AC:
2
AN:
4818
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.000191
AC:
13
AN:
68008
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
3
4
6
7
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:
0.000134
Hom.:
0
Bravo
AF:
0.000128
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000741
AC:
9
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 05, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.625G>A (p.V209I) alteration is located in exon 1 (coding exon 1) of the OR6S1 gene. This alteration results from a G to A substitution at nucleotide position 625, causing the valine (V) at amino acid position 209 to be replaced by an isoleucine (I). 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
0.12
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0031
T
Eigen
Benign
-0.078
Eigen_PC
Benign
-0.0034
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.36
T
MutationAssessor
Benign
0.40
N
PhyloP100
-0.088
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.40
N
REVEL
Benign
0.12
Sift
Benign
0.14
T
Sift4G
Benign
0.24
T
Polyphen
0.86
P
Vest4
0.067
MVP
0.28
MPC
0.11
ClinPred
0.19
T
GERP RS
4.7
Varity_R
0.20
gMVP
0.083
Mutation Taster
=97/3
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: rs150042729; hg19: chr14-21109226; COSMIC: COSV104413472; API