chr11-48264704-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004726.1(OR4X1):​c.844C>G​(p.Pro282Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P282S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

OR4X1
NM_001004726.1 missense

Scores

4
8
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.66
Variant links:
Genes affected
OR4X1 (HGNC:14854): (olfactory receptor family 4 subfamily X 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR4X1NM_001004726.1 linkc.844C>G p.Pro282Ala missense_variant 1/1 ENST00000320048.1 NP_001004726.1 Q8NH49

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR4X1ENST00000320048.1 linkc.844C>G p.Pro282Ala missense_variant 1/16 NM_001004726.1 ENSP00000321506.1 Q8NH49

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.028
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T
Eigen
Pathogenic
0.78
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.043
D
MetaRNN
Uncertain
0.62
D
MetaSVM
Uncertain
0.66
D
MutationAssessor
Pathogenic
4.1
H
PrimateAI
Benign
0.23
T
PROVEAN
Pathogenic
-7.2
D
REVEL
Benign
0.27
Sift
Uncertain
0.0060
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.32
MutPred
0.49
Gain of sheet (P = 0.0827);
MVP
0.88
MPC
0.0077
ClinPred
0.95
D
GERP RS
4.3
Varity_R
0.75
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs10838852; hg19: chr11-48286256; API