11-5778511-T-C

Position:

chr11-5778511-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001385662.1(OR52N5):c.124A>G(p.Met42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,517,520 control chromosomes in the GnomAD database, including 50 homozygotes. 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: 𝑓 0.00022 ( 4 hom., cov: 25)

Exomes 𝑓: 0.00016 ( 46 hom. )

Consequence

OR52N5
NM_001385662.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.493

Variant links:

Genes affected

OR52N5 (HGNC:15231): (olfactory receptor family 52 subfamily N member 5) 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]

OR52N5 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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047756433).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52N5	NM_001385662.1 linkuse as main transcript	c.124A>G	p.Met42Val	missense_variant	3/3	ENST00000641181.1	NP_001372591.1
OR52N5	NM_001001922.2 linkuse as main transcript	c.124A>G	p.Met42Val	missense_variant	1/1		NP_001001922.2	Q8NH56A0A126GVK9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR52N5	ENST00000641181.1 linkuse as main transcript	c.124A>G	p.Met42Val	missense_variant	3/3		NM_001385662.1	ENSP00000493190.1	Q8NH56
TRIM5	ENST00000412903.1 linkuse as main transcript	c.-61-98273A>G		intron_variant		1		ENSP00000388031.1	E7EQQ5
OR52N5	ENST00000317093.2 linkuse as main transcript	c.124A>G	p.Met42Val	missense_variant	1/1	6		ENSP00000322866.2	Q8NH56
TRIM5	ENST00000380027.5 linkuse as main transcript	c.-441+77241A>G		intron_variant		5		ENSP00000369366.1	Q9C035-4

Frequencies

GnomAD3 genomes

AF:

0.000216

AC:

AN:

138710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000740

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000159

Gnomad OTH

AF:

0.000541

GnomAD3 exomes

AF:

0.0000719

AC:

AN:

236444

Hom.:

AF XY:

0.0000470

AC XY:

AN XY:

127748

show subpopulations

Gnomad AFR exome

AF:

0.000642

Gnomad AMR exome

AF:

0.0000309

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:

0.0000562

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000157

AC:

217

AN:

1378810

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

686086

show subpopulations

Gnomad4 AFR exome

AF:

0.000565

Gnomad4 AMR exome

AF:

0.0000238

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:

0.000186

Gnomad4 OTH exome

AF:

0.0000526

GnomAD4 genome

AF:

0.000216

AC:

AN:

138710

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

AN XY:

67456

show subpopulations

Gnomad4 AFR

AF:

0.000740

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000159

Gnomad4 OTH

AF:

0.000541

Alfa

AF:

0.000430

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00118

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000771

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

Mar 01, 2023

The c.124A>G (p.M42V) alteration is located in exon 1 (coding exon 1) of the OR52N5 gene. This alteration results from a A to G substitution at nucleotide position 124, causing the methionine (M) at amino acid position 42 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

0.076

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.0

DANN

Benign

0.88

DEOGEN2

Benign

0.0069

T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.37

.;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.13

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.3

.;N

REVEL

Benign

0.16

Sift

Benign

0.35

.;T

Sift4G

Benign

0.45

.;T

Polyphen

0.085

B;B

Vest4

0.43

MVP

0.22

MPC

0.084

ClinPred

0.024

GERP RS

3.6

Varity_R

0.13

gMVP

0.18

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