11-5777783-G-C

Position:

• chr11-5777783-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001385662.1(OR52N5):​c.852C>G​(p.Ile284Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000362 in 1,381,068 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000036 (2 hom.)
• Consequence: OR52N5 NM_001385662.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.92

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1865905).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52N5	NM_001385662.1	c.852C>G	p.Ile284Met	missense_variant	3/3	ENST00000641181.1	NP_001372591.1
OR52N5	NM_001001922.2	c.852C>G	p.Ile284Met	missense_variant	1/1		NP_001001922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52N5	ENST00000641181.1	c.852C>G	p.Ile284Met	missense_variant	3/3		NM_001385662.1	ENSP00000493190	P1
TRIM5	ENST00000412903.1	c.-61-97545C>G		intron_variant		1		ENSP00000388031
OR52N5	ENST00000317093.2	c.852C>G	p.Ile284Met	missense_variant	1/1			ENSP00000322866	P1
TRIM5	ENST00000380027.5	c.-441+77969C>G		intron_variant		5		ENSP00000369366

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD3 exomes AF: 0.0000170 AC: 4 AN: 235776 Hom.: 2 AF XY: 0.0000157 AC XY: 2 AN XY: 127390

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000619

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: 0.00000362 AC: 5 AN: 1381068 Hom.: 2 Cov.: 30 AF XY: 0.00000437 AC XY: 3 AN XY: 686990

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: 0.00000285

Gnomad4 OTH exome AF: 0.0000350

GnomAD4 genome Cov.: 25

ExAC AF: 0.0000173 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2022

The c.852C>G (p.I284M) alteration is located in exon 1 (coding exon 1) of the OR52N5 gene. This alteration results from a C to G substitution at nucleotide position 852, causing the isoleucine (I) at amino acid position 284 to be replaced by a methionine (M). 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	Benign	0.17
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.040
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-2.8	.;D
REVEL	Benign	0.12
Sift	Pathogenic	0.0	.;D
Sift4G	Uncertain	0.016	.;D
Polyphen		0.94	P;P
Vest4		0.46
MutPred		0.51		Loss of catalytic residue at L289 (P = 0.0318);Loss of catalytic residue at L289 (P = 0.0318);
MVP		0.30
MPC		0.39
ClinPred		0.50	D
GERP RS		0.38
Varity_R		0.37
gMVP		0.099

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

Other links and lift over

dbSNP: rs771965335; hg19: chr11-5799013;