chr11-5777974-A-C

Position:

• chr11-5777974-A-C

Variant summary

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

The NM_001385662.1(OR52N5):​c.661T>G​(p.Cys221Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000329 in 1,519,628 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000028 (1 hom., cov: 26)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: OR52N5 NM_001385662.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.912

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09834051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR52N5	NM_001385662.1	c.661T>G	p.Cys221Gly	missense_variant	3/3	ENST00000641181.1
OR52N5	NM_001001922.2	c.661T>G	p.Cys221Gly	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52N5	ENST00000641181.1	c.661T>G	p.Cys221Gly	missense_variant	3/3		NM_001385662.1	P1
TRIM5	ENST00000412903.1	c.-61-97736T>G		intron_variant		1
OR52N5	ENST00000317093.2	c.661T>G	p.Cys221Gly	missense_variant	1/1			P1
TRIM5	ENST00000380027.5	c.-441+77778T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000284 AC: 4 AN: 140606 Hom.: 1 Cov.: 26

Gnomad AFR AF: 0.000104

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: 0.00

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1379022 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 686108

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: 0.00

Gnomad4 OTH exome AF: 0.0000175

GnomAD4 genome AF: 0.0000284 AC: 4 AN: 140606 Hom.: 1 Cov.: 26 AF XY: 0.0000585 AC XY: 4 AN XY: 68414

Gnomad4 AFR AF: 0.000104

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: 0.00

Bravo AF: 0.0000189

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 03, 2022

The c.661T>G (p.C221G) alteration is located in exon 1 (coding exon 1) of the OR52N5 gene. This alteration results from a T to G substitution at nucleotide position 661, causing the cysteine (C) at amino acid position 221 to be replaced by a glycine (G). 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	0.091
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.71
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.37	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.9	.;D
REVEL	Benign	0.033
Sift	Pathogenic	0.0	.;D
Sift4G	Benign	0.13	.;T
Polyphen		0.15	B;B
Vest4		0.29
MutPred		0.26		Loss of stability (P = 0.046);Loss of stability (P = 0.046);
MVP		0.34
MPC		0.12
ClinPred		0.21	T
GERP RS		-2.9
Varity_R		0.42
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1487120950; hg19: chr11-5799204;