11-5754824-G-C

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001005175.5(OR52N4):c.84G>C(p.Trp28Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

OR52N4
NM_001005175.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.946

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR52N4	NM_001005175.5 link	c.84G>C	p.Trp28Cys	missense_variant	Exon 2 of 2	ENST00000641350.2	NP_001005175.3	Q8NGI2
OR52N4	XM_017017711.3 link	c.84G>C	p.Trp28Cys	missense_variant	Exon 5 of 5		XP_016873200.1	Q8NGI2
OR52N4	XM_017017713.3 link	c.84G>C	p.Trp28Cys	missense_variant	Exon 4 of 4		XP_016873202.1	Q8NGI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR52N4	ENST00000641350.2 link	c.84G>C	p.Trp28Cys	missense_variant	Exon 2 of 2		NM_001005175.5	ENSP00000493338.1	Q8NGI2
TRIM5	ENST00000412903.1 link	c.-61-74586C>G		intron_variant	Intron 2 of 4	1		ENSP00000388031.1	E7EQQ5
TRIM5	ENST00000380027.5 link	c.-440-69430C>G		intron_variant	Intron 3 of 10	5		ENSP00000369366.1	Q9C035-4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461530

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 07, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.84G>C (p.W28C) alteration is located in exon 1 (coding exon 1) of the OR52N4 gene. This alteration results from a G to C substitution at nucleotide position 84, causing the tryptophan (W) at amino acid position 28 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

.;D

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.95

D;D

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-12

.;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0070

.;D

Sift4G

Uncertain

0.0080

.;D

Polyphen

0.75

P;P

Vest4

0.52

MutPred

0.83

Gain of catalytic residue at W28 (P = 0.0998);Gain of catalytic residue at W28 (P = 0.0998);

MVP

0.59

MPC

0.14

ClinPred

1.0

GERP RS

5.9

Varity_R

0.79

gMVP

0.43

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