chr11-5841380-T-G

Position:

• chr11-5841380-T-G

Variant summary

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

The NM_001005167.2(OR52E6):​c.518A>C​(p.His173Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR52E6 NM_001005167.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.889

Genes affected

OR52E6 (HGNC:15215): (olfactory receptor family 52 subfamily E member 6) 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 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=0.19082573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52E6	NM_001005167.2	c.518A>C	p.His173Pro	missense_variant	1/1	ENST00000329322.5	NP_001005167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52E6	ENST00000329322.5	c.518A>C	p.His173Pro	missense_variant	1/1	6	NM_001005167.2	ENSP00000328878.5
TRIM5	ENST00000412903.1	c.-62+96021A>C		intron_variant		1		ENSP00000388031.1
OR52E6	ENST00000379946.2	c.530A>C	p.His177Pro	missense_variant	2/2	6		ENSP00000369279.2
TRIM5	ENST00000380027.5	c.-441+14372A>C		intron_variant		5		ENSP00000369366.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250986 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135612

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 52 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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.: 33

ExAC AF: 0.00000824 AC: 1

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

May 06, 2024

The c.518A>C (p.H173P) alteration is located in exon 1 (coding exon 1) of the OR52E6 gene. This alteration results from a A to C substitution at nucleotide position 518, causing the histidine (H) at amino acid position 173 to be replaced by a proline (P). 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	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.063	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.6	D;D
REVEL	Benign	0.080
Sift	Benign	0.071	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.98	D;.
Vest4		0.42
MutPred		0.30		Gain of relative solvent accessibility (P = 0.0249);.;
MVP		0.27
MPC		0.017
ClinPred		0.62	D
GERP RS		2.3
Varity_R		0.46
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs751367665; hg19: chr11-5862610;