11-5755396-C-T

Position:

chr11-5755396-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001005175.5(OR52N4):c.656C>T(p.Ser219Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00827 in 1,613,994 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 61 hom. )

Consequence

OR52N4
NM_001005175.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.96

Variant links:

Genes affected

OR52N4 (HGNC:15230): (olfactory receptor family 52 subfamily N member 4) 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]

OR52N4 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041511774).

BP6

Variant 11-5755396-C-T is Benign according to our data. Variant chr11-5755396-C-T is described in ClinVar as [Benign]. Clinvar id is 782293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52N4	NM_001005175.5 linkuse as main transcript	c.656C>T	p.Ser219Phe	missense_variant	2/2	ENST00000641350.2	NP_001005175.3	Q8NGI2
OR52N4	XM_017017711.3 linkuse as main transcript	c.656C>T	p.Ser219Phe	missense_variant	5/5		XP_016873200.1	Q8NGI2
OR52N4	XM_017017713.3 linkuse as main transcript	c.656C>T	p.Ser219Phe	missense_variant	4/4		XP_016873202.1	Q8NGI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR52N4	ENST00000641350.2 linkuse as main transcript	c.656C>T	p.Ser219Phe	missense_variant	2/2		NM_001005175.5	ENSP00000493338.1	Q8NGI2
TRIM5	ENST00000412903.1 linkuse as main transcript	c.-61-75158G>A		intron_variant		1		ENSP00000388031.1	E7EQQ5
TRIM5	ENST00000380027.5 linkuse as main transcript	c.-440-70002G>A		intron_variant		5		ENSP00000369366.1	Q9C035-4

Frequencies

GnomAD3 genomes

AF:

0.00624

AC:

950

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00617

AC:

1538

AN:

249446

Hom.:

AF XY:

0.00605

AC XY:

819

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.000708

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00637

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.00941

Gnomad OTH exome

AF:

0.00645

GnomAD4 exome

AF:

0.00849

AC:

12403

AN:

1461728

Hom.:

Cov.:

AF XY:

0.00835

AC XY:

6069

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00631

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.00953

Gnomad4 NFE exome

AF:

0.00992

Gnomad4 OTH exome

AF:

0.00752

GnomAD4 genome

AF:

0.00624

AC:

950

AN:

152266

Hom.:

Cov.:

AF XY:

0.00613

AC XY:

456

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00847

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00849

Hom.:

Bravo

AF:

0.00529

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.000929

AC:

ESP6500EA

AF:

0.00806

AC:

ExAC

AF:

0.00570

AC:

691

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00895

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0059

T;T

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.057

MetaRNN

Benign

0.042

T;T

MetaSVM

Uncertain

0.040

MutationAssessor

Pathogenic

3.9

H;H

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-6.0

.;D

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

1.0

D;D

Vest4

0.70

MVP

0.79

MPC

0.13

ClinPred

0.085

GERP RS

6.1

Varity_R

0.91

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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