11-5857589-G-C

Position:

• chr11-5857589-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005168.3(OR52E8):​c.102C>G​(p.Phe34Leu) 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)
  • Exomes 𝑓: 0.00011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR52E8 NM_001005168.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.37

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.114280164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52E8	NM_001005168.3	c.102C>G	p.Phe34Leu	missense_variant	1/1	ENST00000537935.2	NP_001005168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52E8	ENST00000537935.2	c.102C>G	p.Phe34Leu	missense_variant	1/1	6	NM_001005168.3	ENSP00000444054.2
TRIM5	ENST00000412903.1	c.-62+79812C>G		intron_variant		1		ENSP00000388031.1
TRIM5	ENST00000380027.5	c.-543-1735C>G		intron_variant		5		ENSP00000369366.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000107 AC: 145 AN: 1360576 Hom.: 0 Cov.: 34 AF XY: 0.0000973 AC XY: 66 AN XY: 678092

Gnomad4 AFR exome AF: 0.000277

Gnomad4 AMR exome AF: 0.0000477

Gnomad4 ASJ exome AF: 0.0000893

Gnomad4 EAS exome AF: 0.0000905

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00201

Gnomad4 NFE exome AF: 0.0000353

Gnomad4 OTH exome AF: 0.000130

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 01, 2023

The c.114C>G (p.F38L) 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 114, causing the phenylalanine (F) at amino acid position 38 to be replaced by a leucine (L). 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	0.30
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.6
DANN	Benign	0.87
DEOGEN2	Benign	0.00036	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.020	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.051
Sift	Benign	0.068	T
Sift4G	Benign	0.079	T
Polyphen		0.0010	B
Vest4		0.024
MutPred		0.70		Loss of catalytic residue at P36 (P = 0.0974);
MVP		0.061
MPC		0.0026
ClinPred		0.087	T
GERP RS		-1.3
Varity_R		0.043
gMVP		0.067

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-5878819;