19-15087460-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001004713.2(OR1I1):​c.395A>G​(p.Tyr132Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

OR1I1
NM_001004713.2 missense

Scores

6
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06
Variant links:
Genes affected
OR1I1 (HGNC:8207): (olfactory receptor family 1 subfamily I 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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.775

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR1I1NM_001004713.2 linkuse as main transcriptc.395A>G p.Tyr132Cys missense_variant 2/2 ENST00000641398.1 NP_001004713.1 O60431

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR1I1ENST00000641398.1 linkuse as main transcriptc.395A>G p.Tyr132Cys missense_variant 2/2 NM_001004713.2 ENSP00000493393.1 O60431
OR1I1ENST00000209540.2 linkuse as main transcriptc.395A>G p.Tyr132Cys missense_variant 1/16 ENSP00000209540.2 O60431

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251254
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
59
GnomAD4 genome
Cov.:
33

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 GeneticsDec 06, 2022The c.395A>G (p.Y132C) alteration is located in exon 1 (coding exon 1) of the OR1I1 gene. This alteration results from a A to G substitution at nucleotide position 395, causing the tyrosine (Y) at amino acid position 132 to be replaced by a cysteine (C). 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
0.15
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.13
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T;T
Eigen
Uncertain
0.45
Eigen_PC
Benign
0.21
FATHMM_MKL
Benign
0.35
N
LIST_S2
Benign
0.54
.;T
M_CAP
Benign
0.0087
T
MetaRNN
Pathogenic
0.78
D;D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Pathogenic
3.5
M;M
PrimateAI
Benign
0.32
T
PROVEAN
Pathogenic
-9.0
.;D
REVEL
Uncertain
0.37
Sift
Pathogenic
0.0
.;D
Sift4G
Pathogenic
0.0
.;D
Polyphen
1.0
D;D
Vest4
0.69
MutPred
0.51
Gain of catalytic residue at L133 (P = 0.0117);Gain of catalytic residue at L133 (P = 0.0117);
MVP
0.46
MPC
0.32
ClinPred
0.91
D
GERP RS
3.8
Varity_R
0.76
gMVP
0.48

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: rs201465347; hg19: chr19-15198271; API