11-5857379-G-C

Position:

chr11-5857379-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001005168.3(OR52E8):c.312C>G(p.Phe104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,610,242 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0040 ( 52 hom. )

Consequence

OR52E8
NM_001005168.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.171

Variant links:

Genes affected

OR52E8 (HGNC:15217): (olfactory receptor family 52 subfamily E member 8) 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]

OR52E8 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054122508).

BP6

Variant 11-5857379-G-C is Benign according to our data. Variant chr11-5857379-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2641544.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-5857379-G-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52E8	NM_001005168.3 linkuse as main transcript	c.312C>G	p.Phe104Leu	missense_variant	1/1	ENST00000537935.2	NP_001005168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52E8	ENST00000537935.2 linkuse as main transcript	c.312C>G	p.Phe104Leu	missense_variant	1/1		NM_001005168.3	ENSP00000444054	P1
TRIM5	ENST00000412903.1 linkuse as main transcript	c.-62+80022C>G		intron_variant		1		ENSP00000388031
TRIM5	ENST00000380027.5 linkuse as main transcript	c.-543-1525C>G		intron_variant		5		ENSP00000369366		Q9C035-4

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

552

AN:

149674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000819

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00454

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00422

Gnomad OTH

AF:

0.00627

GnomAD3 exomes

AF:

0.00440

AC:

1102

AN:

250500

Hom.:

AF XY:

0.00435

AC XY:

589

AN XY:

135482

show subpopulations

Gnomad AFR exome

AF:

0.000894

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.0332

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.00203

Gnomad NFE exome

AF:

0.00465

Gnomad OTH exome

AF:

0.00767

GnomAD4 exome

AF:

0.00397

AC:

5797

AN:

1460456

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

2945

AN XY:

726642

show subpopulations

Gnomad4 AFR exome

AF:

0.000897

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.0336

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00226

Gnomad4 FIN exome

AF:

0.00167

Gnomad4 NFE exome

AF:

0.00364

Gnomad4 OTH exome

AF:

0.00635

GnomAD4 genome

AF:

0.00369

AC:

552

AN:

149786

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

246

AN XY:

73316

show subpopulations

Gnomad4 AFR

AF:

0.000816

Gnomad4 AMR

AF:

0.00454

Gnomad4 ASJ

AF:

0.0351

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00422

Gnomad4 OTH

AF:

0.00621

Alfa

AF:

0.00683

Hom.:

Bravo

AF:

0.00377

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000465

AC:

ESP6500EA

AF:

0.00582

AC:

ExAC

AF:

0.00421

AC:

510

Asia WGS

AF:

0.00174

AC:

AN:

3466

EpiCase

AF:

0.00540

EpiControl

AF:

0.00640

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

TRIM5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0094

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.73

M_CAP

Benign

0.025

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-5.6

REVEL

Benign

0.13

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0040

Polyphen

0.34

Vest4

0.34

MutPred

0.32

Loss of stability (P = 0.4491);

MVP

0.18

MPC

0.0038

ClinPred

0.064

GERP RS

4.2

Varity_R

0.70

gMVP

0.088

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

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