11-5788356-C-T

Variant summary

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

The NM_001001913.2(OR52N1):​c.461G>A​(p.Gly154Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

OR52N1
NM_001001913.2 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0360
Variant links:
Genes affected
OR52N1 (HGNC:14853): (olfactory receptor family 52 subfamily N 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]
TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

Genome browser will be placed here

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
OR52N1NM_001001913.2 linkuse as main transcriptc.461G>A p.Gly154Asp missense_variant 2/2 ENST00000641645.1 NP_001001913.1 Q8NH53

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR52N1ENST00000641645.1 linkuse as main transcriptc.461G>A p.Gly154Asp missense_variant 2/2 NM_001001913.2 ENSP00000493272.1 Q8NH53
TRIM5ENST00000412903.1 linkuse as main transcriptc.-61-108118G>A intron_variant 1 ENSP00000388031.1 E7EQQ5
TRIM5ENST00000380027.5 linkuse as main transcriptc.-441+67396G>A intron_variant 5 ENSP00000369366.1 Q9C035-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
250474
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135350
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000203
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
AF:
0.00000547
AC:
8
AN:
1461738
Hom.:
0
Cov.:
65
AF XY:
0.00000550
AC XY:
4
AN XY:
727170
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1

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 04, 2022The c.461G>A (p.G154D) alteration is located in exon 1 (coding exon 1) of the OR52N1 gene. This alteration results from a G to A substitution at nucleotide position 461, causing the glycine (G) at amino acid position 154 to be replaced by an aspartic acid (D). 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
0.21
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.014
T;T
Eigen
Uncertain
0.23
Eigen_PC
Benign
0.038
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.54
.;T
M_CAP
Benign
0.0074
T
MetaRNN
Uncertain
0.68
D;D
MetaSVM
Benign
-0.49
T
MutationAssessor
Pathogenic
3.2
M;M
PrimateAI
Benign
0.22
T
PROVEAN
Uncertain
-3.9
.;D
REVEL
Benign
0.28
Sift
Uncertain
0.0020
.;D
Sift4G
Uncertain
0.0060
.;D
Polyphen
0.78
P;P
Vest4
0.37
MutPred
0.78
Loss of methylation at R153 (P = 0.0391);Loss of methylation at R153 (P = 0.0391);
MVP
0.61
MPC
0.21
ClinPred
0.83
D
GERP RS
4.6
Varity_R
0.57
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs746238148; hg19: chr11-5809586; API