chr11-5788014-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001001913.2(OR52N1):c.803G>A(p.Gly268Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,298,904 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G268R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00030 ( 1 hom., cov: 24)

Exomes 𝑓: 0.000012 ( 2 hom. )

Consequence

OR52N1
NM_001001913.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.18

Publications

1 publications found

Variant links:

Genes affected

OR52N1 (HGNC:14853): (olfactory receptor family 52 subfamily N member 1) 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]

OR52N1 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021604389).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001913.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52N1	NM_001001913.2	MANE Select	c.803G>A	p.Gly268Glu	missense	Exon 2 of 2	NP_001001913.1	Q8NH53

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR52N1	ENST00000641645.1	MANE Select	c.803G>A	p.Gly268Glu	missense	Exon 2 of 2	ENSP00000493272.1	Q8NH53
TRIM5	ENST00000412903.1	TSL:1	c.-61-107776G>A		intron	N/A	ENSP00000388031.1	E7EQQ5
TRIM5	ENST00000957480.1		c.-62+20885G>A		intron	N/A	ENSP00000627539.1

Frequencies

GnomAD3 genomes

AF:

0.000299

AC:

AN:

90206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00105

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000864

AC:

AN:

196744

AF XY:

0.0000749

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1208698

Hom.:

Cov.:

AF XY:

0.00000833

AC XY:

AN XY:

600478

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

27710

American (AMR)

AF:

0.00

AC:

AN:

35882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20196

East Asian (EAS)

AF:

0.00

AC:

AN:

31758

South Asian (SAS)

AF:

0.00

AC:

AN:

68270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4342

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

933256

Other (OTH)

AF:

0.0000415

AC:

AN:

48244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000299

AC:

AN:

90206

Hom.:

Cov.:

AF XY:

0.000342

AC XY:

AN XY:

43860

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

25776

American (AMR)

AF:

0.00

AC:

AN:

8422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1970

East Asian (EAS)

AF:

0.00

AC:

AN:

3260

South Asian (SAS)

AF:

0.00

AC:

AN:

2904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

158

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

39940

Other (OTH)

AF:

0.00

AC:

AN:

1216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000234

ESP6500AA

AF:

0.00212

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000861

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.4

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0021

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.57

M_CAP

Benign

0.011

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

-1.2

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.69

REVEL

Benign

0.063

Sift

Benign

0.055

Sift4G

Benign

0.54

Polyphen

0.0060

Vest4

0.18

MVP

0.42

MPC

0.052

ClinPred

0.036

GERP RS

3.8

Varity_R

0.032

gMVP

0.22

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over