11-5778397-G-C

Position:

• chr11-5778397-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001385662.1(OR52N5):​c.238C>G​(p.Leu80Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: OR52N5 NM_001385662.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.43

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065779746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52N5	NM_001385662.1	c.238C>G	p.Leu80Val	missense_variant	3/3	ENST00000641181.1	NP_001372591.1
OR52N5	NM_001001922.2	c.238C>G	p.Leu80Val	missense_variant	1/1		NP_001001922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52N5	ENST00000641181.1	c.238C>G	p.Leu80Val	missense_variant	3/3		NM_001385662.1	ENSP00000493190.1
TRIM5	ENST00000412903.1	c.-61-98159C>G		intron_variant		1		ENSP00000388031.1
OR52N5	ENST00000317093.2	c.238C>G	p.Leu80Val	missense_variant	1/1	6		ENSP00000322866.2
TRIM5	ENST00000380027.5	c.-441+77355C>G		intron_variant		5		ENSP00000369366.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381266 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 687076

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: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Sep 05, 2024

The c.238C>G (p.L80V) 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 238, causing the leucine (L) at amino acid position 80 to be replaced by a valine (V). 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	0.093
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.12
DANN	Benign	0.88
DEOGEN2	Benign	0.0051	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.57	.;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.022
Sift	Benign	0.27	.;T
Sift4G	Benign	0.18	.;T
Polyphen		0.0	B;B
Vest4		0.16
MutPred		0.56		Loss of stability (P = 0.1363);Loss of stability (P = 0.1363);
MVP		0.12
MPC		0.066
ClinPred		0.15	T
GERP RS		1.6
Varity_R		0.052
gMVP		0.058

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-5799627;