11-5841185-G-A

Position:

chr11-5841185-G-A

Variant summary

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

The NM_001005167.2(OR52E6):c.713C>T(p.Ala238Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

OR52E6
NM_001005167.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Variant links:

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]

OR52E6 links:

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]

TRIM5 links:

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
OR52E6	NM_001005167.2 linkuse as main transcript	c.713C>T	p.Ala238Val	missense_variant	1/1	ENST00000329322.5	NP_001005167.1	Q96RD3A0A126GVK5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR52E6	ENST00000329322.5 linkuse as main transcript	c.713C>T	p.Ala238Val	missense_variant	1/1	6	NM_001005167.2	ENSP00000328878.5	Q96RD3
TRIM5	ENST00000412903.1 linkuse as main transcript	c.-62+96216C>T		intron_variant		1		ENSP00000388031.1	E7EQQ5
OR52E6	ENST00000379946.2 linkuse as main transcript	c.725C>T	p.Ala242Val	missense_variant	2/2	6		ENSP00000369279.2	J3KPH0
TRIM5	ENST00000380027.5 linkuse as main transcript	c.-441+14567C>T		intron_variant		5		ENSP00000369366.1	Q9C035-4

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249532

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00000887

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461580

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727090

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000204

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000344

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Jul 08, 2021

The c.713C>T (p.A238V) alteration is located in exon 1 (coding exon 1) of the OR52E6 gene. This alteration results from a C to T substitution at nucleotide position 713, causing the alanine (A) at amino acid position 238 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

-0.23

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

-0.0015

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.69

MutationAssessor

Pathogenic

3.0

M;.

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

1.0

D;.

Vest4

0.54

MutPred

0.68

Gain of methylation at K237 (P = 0.0354);.;

MVP

0.40

MPC

0.027

ClinPred

0.96

GERP RS

2.5

Varity_R

0.43

gMVP

0.16

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over