chr1-158547801-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001005189.2(OR6Y1):​c.305G>T​(p.Cys102Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,613,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C102Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

OR6Y1
NM_001005189.2 missense

Scores

10
2
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.79
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR6Y1NM_001005189.2 linkuse as main transcriptc.305G>T p.Cys102Phe missense_variant 2/2 ENST00000641622.1
OR6Y1NM_001386050.1 linkuse as main transcriptc.305G>T p.Cys102Phe missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR6Y1ENST00000641622.1 linkuse as main transcriptc.305G>T p.Cys102Phe missense_variant 2/2 NM_001005189.2 P1
OR6Y1ENST00000641282.1 linkuse as main transcriptc.305G>T p.Cys102Phe missense_variant 2/2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000725
AC:
11
AN:
151632
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000598
AC:
15
AN:
250890
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135566
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000124
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000209
AC:
306
AN:
1461724
Hom.:
0
Cov.:
33
AF XY:
0.000179
AC XY:
130
AN XY:
727170
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000262
Gnomad4 OTH exome
AF:
0.000248
GnomAD4 genome
AF:
0.0000725
AC:
11
AN:
151632
Hom.:
0
Cov.:
32
AF XY:
0.0000540
AC XY:
4
AN XY:
74090
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000128
Hom.:
0
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000237

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 GeneticsMay 30, 2024The c.305G>T (p.C102F) alteration is located in exon 1 (coding exon 1) of the OR6Y1 gene. This alteration results from a G to T substitution at nucleotide position 305, causing the cysteine (C) at amino acid position 102 to be replaced by a phenylalanine (F). 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
Pathogenic
0.57
BayesDel_addAF
Benign
-0.040
T
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.059
T;T;T
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.87
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
.;.;D
M_CAP
Benign
0.0090
T
MetaRNN
Pathogenic
0.87
D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
4.4
H;H;H
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.34
T
PROVEAN
Pathogenic
-9.7
.;.;D
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
.;.;D
Sift4G
Pathogenic
0.0
.;.;D
Polyphen
1.0
D;D;D
Vest4
0.84
MVP
0.65
MPC
0.17
ClinPred
1.0
D
GERP RS
4.9
Varity_R
0.99
gMVP
0.46

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: rs149059042; hg19: chr1-158517591; API