chr11-5777934-G-A

Position:

chr11-5777934-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001385662.1(OR52N5):c.701C>T(p.Ala234Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000625 in 1,520,940 control chromosomes in the GnomAD database, including 18 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000067 ( 18 hom. )

Consequence

OR52N5
NM_001385662.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.55

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=0.07956579).

BP6

Variant 11-5777934-G-A is Benign according to our data. Variant chr11-5777934-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2349114.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52N5	NM_001385662.1 linkuse as main transcript	c.701C>T	p.Ala234Val	missense_variant	3/3	ENST00000641181.1	NP_001372591.1
OR52N5	NM_001001922.2 linkuse as main transcript	c.701C>T	p.Ala234Val	missense_variant	1/1		NP_001001922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52N5	ENST00000641181.1 linkuse as main transcript	c.701C>T	p.Ala234Val	missense_variant	3/3		NM_001385662.1	ENSP00000493190	P1
TRIM5	ENST00000412903.1 linkuse as main transcript	c.-61-97696C>T		intron_variant		1		ENSP00000388031
OR52N5	ENST00000317093.2 linkuse as main transcript	c.701C>T	p.Ala234Val	missense_variant	1/1			ENSP00000322866	P1
TRIM5	ENST00000380027.5 linkuse as main transcript	c.-441+77818C>T		intron_variant		5		ENSP00000369366		Q9C035-4

Frequencies

GnomAD3 genomes

AF:

0.0000214

AC:

AN:

140190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000261

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:

0.0000316

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000850

AC:

AN:

235358

Hom.:

AF XY:

0.00000786

AC XY:

AN XY:

127192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000666

AC:

AN:

1380750

Hom.:

Cov.:

AF XY:

0.0000582

AC XY:

AN XY:

686918

show subpopulations

Gnomad4 AFR exome

AF:

0.0000314

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000818

Gnomad4 OTH exome

AF:

0.0000701

GnomAD4 genome

AF:

0.0000214

AC:

AN:

140190

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

68198

show subpopulations

Gnomad4 AFR

AF:

0.0000261

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:

0.0000316

Gnomad4 OTH

AF:

0.00

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

Asia WGS

AF:

0.000609

AC:

AN:

3298

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2021

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

0.082

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.4

DANN

Benign

0.63

DEOGEN2

Benign

0.00055

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.080

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-3.8

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

3.9

.;N

REVEL

Benign

0.14

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0020

B;B

Vest4

0.16

MutPred

0.67

Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);

MVP

0.055

MPC

0.065

ClinPred

0.031

GERP RS

2.6

Varity_R

0.026

gMVP

0.062

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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