Genetic Variant OR52B6:p.Ser94Phe (chr11-5581157-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001005162.2(OR52B6):c.281C>T(p.Ser94Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

OR52B6
NM_001005162.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00900

Variant links:

Genes affected

OR52B6 (HGNC:15211): (olfactory receptor family 52 subfamily B 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]

OR52B6 links:

ENSG00000239920 (HGNC:):

ENSG00000239920 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37019312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR52B6	NM_001005162.2 link	c.281C>T	p.Ser94Phe	missense_variant	Exon 1 of 1	ENST00000345043.2	NP_001005162.2	Q8NGF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR52B6	ENST00000345043.2 link	c.281C>T	p.Ser94Phe	missense_variant	Exon 1 of 1	6	NM_001005162.2	ENSP00000341581.2	Q8NGF0
ENSG00000239920	ENST00000380259.7 link	n.*739+9668G>A		intron_variant	Intron 5 of 7	5		ENSP00000369609.3	A0A2U3TZJ3
ENSG00000239920	ENST00000394793.3 link	n.256-8558G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249194

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135100

show subpopulations

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461064

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.281C>T (p.S94F) alteration is located in exon 1 (coding exon 1) of the OR52B6 gene. This alteration results from a C to T substitution at nucleotide position 281, causing the serine (S) at amino acid position 94 to be replaced by a phenylalanine (F). 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

0.24

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.0052

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0016

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.23

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.30

MutPred

0.62

Loss of glycosylation at S94 (P = 0.0322);

MVP

0.51

MPC

0.19

ClinPred

0.77

GERP RS

4.2

Varity_R

0.88

gMVP

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over