chr11-5777785-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001385662.1(OR52N5):c.850A>G(p.Ile284Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000717 in 139,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I284M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000072 ( 0 hom., cov: 25)

Consequence

OR52N5
NM_001385662.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0350

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058783323).

BP6

Variant 11-5777785-T-C is Benign according to our data. Variant chr11-5777785-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3206025.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR52N5	NM_001385662.1 link	c.850A>G	p.Ile284Val	missense_variant	Exon 3 of 3	ENST00000641181.1	NP_001372591.1
OR52N5	NM_001001922.2 link	c.850A>G	p.Ile284Val	missense_variant	Exon 1 of 1		NP_001001922.2	Q8NH56A0A126GVK9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR52N5	ENST00000641181.1 link	c.850A>G	p.Ile284Val	missense_variant	Exon 3 of 3		NM_001385662.1	ENSP00000493190.1	Q8NH56
TRIM5	ENST00000412903.1 link	c.-61-97547A>G		intron_variant	Intron 2 of 4	1		ENSP00000388031.1	E7EQQ5
OR52N5	ENST00000317093.2 link	c.850A>G	p.Ile284Val	missense_variant	Exon 1 of 1	6		ENSP00000322866.2	Q8NH56
TRIM5	ENST00000380027.5 link	c.-441+77967A>G		intron_variant	Intron 3 of 10	5		ENSP00000369366.1	Q9C035-4

Frequencies

GnomAD3 genomes

AF:

0.00000718

AC:

AN:

139338

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000158

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000848

AC:

AN:

235792

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000115

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000717

AC:

AN:

139462

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

67860

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38084

American (AMR)

AF:

0.00

AC:

AN:

13498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3254

East Asian (EAS)

AF:

0.00

AC:

AN:

4788

South Asian (SAS)

AF:

0.00

AC:

AN:

4264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0000158

AC:

AN:

63174

Other (OTH)

AF:

0.00

AC:

AN:

1860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.00000866

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 16, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.3

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0019

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

PhyloP100

-0.035

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.93

.;N

REVEL

Benign

0.040

Sift

Uncertain

0.019

.;D

Sift4G

Benign

0.093

.;T

Polyphen

0.0050

B;B

Vest4

0.11

MutPred

0.48

Loss of catalytic residue at L289 (P = 0.0334);Loss of catalytic residue at L289 (P = 0.0334);

MVP

0.13

MPC

0.075

ClinPred

0.039

GERP RS

1.4

Varity_R

0.14

gMVP

0.043

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over