rs746238148

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-5788356-C-A
• chr11-5788356-C-G
• chr11-5788356-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001001913.2(OR52N1):​c.461G>T​(p.Gly154Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,816 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G154D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (1 hom.)
• Consequence: OR52N1 NM_001001913.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001913.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52N1	NM_001001913.2	MANE Select	c.461G>T	p.Gly154Val	missense	Exon 2 of 2	NP_001001913.1	Q8NH53

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52N1	ENST00000641645.1	MANE Select	c.461G>T	p.Gly154Val	missense	Exon 2 of 2	ENSP00000493272.1	Q8NH53
	TRIM5	ENST00000412903.1	TSL:1	c.-61-108118G>T		intron	N/A	ENSP00000388031.1	E7EQQ5
	TRIM5	ENST00000957480.1		c.-62+20543G>T		intron	N/A	ENSP00000627539.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250474 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000342 AC: 5 AN: 1461738 Hom.: 1 Cov.: 65 AF XY: 0.00000413 AC XY: 3 AN XY: 727170

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152078 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74278

African (AFR) AF: 0.0000242 AC: 1 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.036
PrimateAI	Benign	0.20	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.21
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.051	T
Polyphen		0.032	B
Vest4		0.15
MutPred		0.70		Loss of methylation at R153 (P = 0.0491)
MVP		0.54
MPC		0.057
ClinPred		0.48	T
GERP RS		4.6
Varity_R		0.52
gMVP		0.45
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs746238148; hg19: chr11-5809586;