chr11-5788038-G-A

Position:

• chr11-5788038-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001913.2(OR52N1):​c.779C>T​(p.Thr260Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,139,716 control chromosomes in the GnomAD database, including 1 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: 𝑓 0.000011 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000029 (1 hom.)
• Consequence: OR52N1 NM_001001913.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.177

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19386142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52N1	NM_001001913.2	c.779C>T	p.Thr260Ile	missense_variant	2/2	ENST00000641645.1	NP_001001913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52N1	ENST00000641645.1	c.779C>T	p.Thr260Ile	missense_variant	2/2		NM_001001913.2	ENSP00000493272	P1
TRIM5	ENST00000412903.1	c.-61-107800C>T		intron_variant		1		ENSP00000388031
TRIM5	ENST00000380027.5	c.-441+67714C>T		intron_variant		5		ENSP00000369366

Frequencies

GnomAD3 genomes AF: 0.0000111 AC: 1 AN: 90110 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000826

GnomAD4 exome AF: 0.00000286 AC: 3 AN: 1049606 Hom.: 1 Cov.: 31 AF XY: 0.00000382 AC XY: 2 AN XY: 523056

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: 0.00000251

Gnomad4 OTH exome AF: 0.0000233

GnomAD4 genome AF: 0.0000111 AC: 1 AN: 90110 Hom.: 0 Cov.: 25 AF XY: 0.0000228 AC XY: 1 AN XY: 43804

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

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: 0.000826

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 29, 2023

The c.779C>T (p.T260I) alteration is located in exon 1 (coding exon 1) of the OR52N1 gene. This alteration results from a C to T substitution at nucleotide position 779, causing the threonine (T) at amino acid position 260 to be replaced by an isoleucine (I). 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	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.5	.;D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.012	.;D
Polyphen		0.92	P;P
Vest4		0.11
MutPred		0.35		Loss of catalytic residue at T260 (P = 0.1281);Loss of catalytic residue at T260 (P = 0.1281);
MVP		0.48
MPC		0.27
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.33
gMVP		0.097

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: rs1261272314; hg19: chr11-5809268;