11-5857419-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005168.3(OR52E8):​c.272C>G​(p.Thr91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

OR52E8
NM_001005168.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.710
Variant links:
Genes affected
OR52E8 (HGNC:15217): (olfactory receptor family 52 subfamily E member 8) 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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05863163).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR52E8NM_001005168.3 linkuse as main transcriptc.272C>G p.Thr91Ser missense_variant 1/1 ENST00000537935.2 NP_001005168.2 Q6IFG1A0A126GVH0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR52E8ENST00000537935.2 linkuse as main transcriptc.272C>G p.Thr91Ser missense_variant 1/16 NM_001005168.3 ENSP00000444054.2 Q6IFG1
TRIM5ENST00000412903.1 linkuse as main transcriptc.-62+79982C>G intron_variant 1 ENSP00000388031.1 E7EQQ5
TRIM5ENST00000380027.5 linkuse as main transcriptc.-543-1565C>G intron_variant 5 ENSP00000369366.1 Q9C035-4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

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 GeneticsMar 28, 2024The c.284C>G (p.T95S) alteration is located in exon 1 (coding exon 1) of the OR52E8 gene. This alteration results from a C to G substitution at nucleotide position 284, causing the threonine (T) at amino acid position 95 to be replaced by a serine (S). 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
0.081
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.87
CADD
Benign
5.7
DANN
Benign
0.43
DEOGEN2
Benign
0.00068
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.064
N
LIST_S2
Benign
0.11
T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
-0.92
N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.29
N
REVEL
Benign
0.020
Sift
Benign
0.40
T
Sift4G
Benign
0.68
T
Polyphen
0.0
B
Vest4
0.055
MutPred
0.24
Loss of catalytic residue at T95 (P = 0.0916);
MVP
0.076
MPC
0.0030
ClinPred
0.33
T
GERP RS
1.8
Varity_R
0.036
gMVP
0.035

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: rs1241868070; hg19: chr11-5878649; COSMIC: COSV101190515; API