11-5788356-C-T

Variant names:

• chr11-5788356-C-T
• rs746238148
• NM_001001913.2:c.461G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001001913.2(OR52N1):​c.461G>A​(p.Gly154Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: OR52N1 NM_001001913.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0360

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]

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR52N1	NM_001001913.2	c.461G>A	p.Gly154Asp	missense_variant	Exon 2 of 2	ENST00000641645.1	NP_001001913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR52N1	ENST00000641645.1	c.461G>A	p.Gly154Asp	missense_variant	Exon 2 of 2		NM_001001913.2	ENSP00000493272.1
TRIM5	ENST00000412903.1	c.-61-108118G>A		intron_variant	Intron 2 of 4	1		ENSP00000388031.1
TRIM5	ENST00000380027.5	c.-441+67396G>A		intron_variant	Intron 3 of 10	5		ENSP00000369366.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000279 AC: 7 AN: 250474 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135350

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000203

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461738 Hom.: 0 Cov.: 65 AF XY: 0.00000550 AC XY: 4 AN XY: 727170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.461G>A (p.G154D) alteration is located in exon 1 (coding exon 1) of the OR52N1 gene. This alteration results from a G to A substitution at nucleotide position 461, causing the glycine (G) at amino acid position 154 to be replaced by an aspartic acid (D). 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	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.038
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.54	.;T
M_CAP	Benign	0.0074	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.9	.;D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0060	.;D
Polyphen		0.78	P;P
Vest4		0.37
MutPred		0.78		Loss of methylation at R153 (P = 0.0391);Loss of methylation at R153 (P = 0.0391);
MVP		0.61
MPC		0.21
ClinPred		0.83	D
GERP RS		4.6
Varity_R		0.57
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs746238148; hg19: chr11-5809586;