11-5884431-A-G

Variant names:

• chr11-5884431-A-G
• rs112835699
• NM_001005165.2:c.139A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005165.2(OR52E4):​c.139A>G​(p.Ile47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,336 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: OR52E4 NM_001005165.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.426

Genes affected

OR52E4 (HGNC:15213): (olfactory receptor family 52 subfamily E member 4) 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]

LOC112268071 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0877299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR52E4	NM_001005165.2	c.139A>G	p.Ile47Val	missense_variant	Exon 2 of 2	ENST00000641726.1	NP_001005165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR52E4	ENST00000641726.1	c.139A>G	p.Ile47Val	missense_variant	Exon 2 of 2		NM_001005165.2	ENSP00000493085.1
TRIM5	ENST00000412903.1	c.-62+52970T>C		intron_variant	Intron 2 of 4	1		ENSP00000388031.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461336 Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8 AN XY: 726988

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000133

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.139A>G (p.I47V) alteration is located in exon 1 (coding exon 1) of the OR52E4 gene. This alteration results from a A to G substitution at nucleotide position 139, causing the isoleucine (I) at amino acid position 47 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.9
DANN	Benign	0.72
DEOGEN2	Benign	0.0028	T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.79	.;N
REVEL	Benign	0.079
Sift	Benign	0.069	.;T
Sift4G	Benign	0.13	.;T
Polyphen		0.0020	B;B
Vest4		0.046
MutPred		0.41		Loss of methylation at K52 (P = 0.1386);Loss of methylation at K52 (P = 0.1386);
MVP		0.20
MPC		0.015
ClinPred		0.11	T
GERP RS		3.9
Varity_R		0.091
gMVP		0.044

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

Other links and lift over

dbSNP: rs112835699; hg19: chr11-5905661;