chr11-5841008-G-C

Variant names:

• chr11-5841008-G-C
• rs61739213
• NM_001005167.2:c.890C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005167.2(OR52E6):​c.890C>G​(p.Thr297Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,607,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. T297I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OR52E6 NM_001005167.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 3 publications found

Genes affected

OR52E6 (HGNC:15215): (olfactory receptor family 52 subfamily E member 6) 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18807784).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005167.2. 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
	OR52E6	NM_001005167.2	MANE Select	c.890C>G	p.Thr297Ser	missense	Exon 1 of 1	NP_001005167.1	A0A126GVK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52E6	ENST00000329322.5	TSL:6 MANE Select	c.890C>G	p.Thr297Ser	missense	Exon 1 of 1	ENSP00000328878.5	Q96RD3
	TRIM5	ENST00000412903.1	TSL:1	c.-62+96393C>G		intron	N/A	ENSP00000388031.1	E7EQQ5
	OR52E6	ENST00000379946.2	TSL:6	c.902C>G	p.Thr301Ser	missense	Exon 2 of 2	ENSP00000369279.2	J3KPH0

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152056 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455142 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723538

African (AFR) AF: 0.00 AC: 0 AN: 33282

American (AMR) AF: 0.00 AC: 0 AN: 43904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25534

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 84914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109042

Other (OTH) AF: 0.00 AC: 0 AN: 60070

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152056 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74288

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.72
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.34
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.18
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.015	D
Polyphen		0.77	P
Vest4		0.089
MutPred		0.70		Loss of catalytic residue at T297 (P = 0.0348)
MVP		0.20
MPC		0.0070
ClinPred		0.80	D
GERP RS		2.5
Varity_R		0.33
gMVP		0.059
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs61739213; hg19: chr11-5862238;