11-5777730-T-C

Position:

• chr11-5777730-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_Strong BS2

The NM_001385662.1(OR52N5):​c.905A>G​(p.Tyr302Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000872 in 1,375,384 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000087 (2 hom.)
• Consequence: OR52N5 NM_001385662.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71

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 Uncertain_significance. Variant got 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.946
• 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.905A>G	p.Tyr302Cys	missense_variant	3/3	ENST00000641181.1	NP_001372591.1
OR52N5	NM_001001922.2	c.905A>G	p.Tyr302Cys	missense_variant	1/1		NP_001001922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52N5	ENST00000641181.1	c.905A>G	p.Tyr302Cys	missense_variant	3/3		NM_001385662.1	ENSP00000493190.1
TRIM5	ENST00000412903.1	c.-61-97492A>G		intron_variant		1		ENSP00000388031.1
OR52N5	ENST00000317093.2	c.905A>G	p.Tyr302Cys	missense_variant	1/1	6		ENSP00000322866.2
TRIM5	ENST00000380027.5	c.-441+78022A>G		intron_variant		5		ENSP00000369366.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000872 AC: 12 AN: 1375384 Hom.: 2 Cov.: 29 AF XY: 0.00000877 AC XY: 6 AN XY: 684200

Gnomad4 AFR exome AF: 0.0000631

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: 0.00000764

Gnomad4 OTH exome AF: 0.0000352

GnomAD4 genome Cov.: 25

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

Oct 02, 2023

The c.905A>G (p.Y302C) alteration is located in exon 1 (coding exon 1) of the OR52N5 gene. This alteration results from a A to G substitution at nucleotide position 905, causing the tyrosine (Y) at amino acid position 302 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	Benign	0.17
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Pathogenic	4.6	H;H
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-8.3	.;D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		1.0	D;D
Vest4		0.73
MutPred		0.78		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.82
MPC		0.44
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.84
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-5798960;