1-158547627-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001005189.2(OR6Y1):​c.479C>T​(p.Thr160Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,613,320 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

OR6Y1
NM_001005189.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0770
Variant links:
Genes affected
OR6Y1 (HGNC:14823): (olfactory receptor family 6 subfamily Y 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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.02050516).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR6Y1NM_001005189.2 linkuse as main transcriptc.479C>T p.Thr160Ile missense_variant 2/2 ENST00000641622.1 NP_001005189.1
OR6Y1NM_001386050.1 linkuse as main transcriptc.479C>T p.Thr160Ile missense_variant 2/2 NP_001372979.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR6Y1ENST00000641622.1 linkuse as main transcriptc.479C>T p.Thr160Ile missense_variant 2/2 NM_001005189.2 ENSP00000492894 P1
OR6Y1ENST00000641282.1 linkuse as main transcriptc.479C>T p.Thr160Ile missense_variant 2/2 ENSP00000493253 P1

Frequencies

GnomAD3 genomes
AF:
0.000152
AC:
23
AN:
151658
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000263
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.000327
AC:
82
AN:
250648
Hom.:
0
AF XY:
0.000384
AC XY:
52
AN XY:
135494
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000436
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00118
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000238
Gnomad OTH exome
AF:
0.000656
GnomAD4 exome
AF:
0.000225
AC:
329
AN:
1461548
Hom.:
2
Cov.:
33
AF XY:
0.000257
AC XY:
187
AN XY:
727048
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000381
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000135
Gnomad4 OTH exome
AF:
0.000530
GnomAD4 genome
AF:
0.000152
AC:
23
AN:
151772
Hom.:
0
Cov.:
32
AF XY:
0.000215
AC XY:
16
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.000475
Alfa
AF:
0.000195
Hom.:
0
Bravo
AF:
0.000147
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000338
AC:
41
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000416

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 26, 2023The c.479C>T (p.T160I) alteration is located in exon 1 (coding exon 1) of the OR6Y1 gene. This alteration results from a C to T substitution at nucleotide position 479, causing the threonine (T) at amino acid position 160 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
0.18
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0013
T;T;T
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.089
N
LIST_S2
Benign
0.39
.;.;T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.021
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.57
N;N;N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
2.7
.;.;N
REVEL
Benign
0.20
Sift
Benign
0.89
.;.;T
Sift4G
Benign
0.69
.;.;T
Polyphen
1.0
D;D;D
Vest4
0.12
MVP
0.49
MPC
0.15
ClinPred
0.093
T
GERP RS
3.4
Varity_R
0.043
gMVP
0.15

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: rs148583112; hg19: chr1-158517417; API