11-6169564-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004052.1(OR52B2):​c.763G>T​(p.Val255Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

OR52B2
NM_001004052.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.704
Variant links:
Genes affected
OR52B2 (HGNC:15207): (olfactory receptor family 52 subfamily B member 2) 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]

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ACMG classification

Classification made for transcript

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=0.10418862).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR52B2NM_001004052.1 linkc.763G>T p.Val255Phe missense_variant Exon 1 of 1 ENST00000530810.2 NP_001004052.1 Q96RD2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR52B2ENST00000530810.2 linkc.763G>T p.Val255Phe missense_variant Exon 1 of 1 6 NM_001004052.1 ENSP00000432011.1 Q96RD2
ENSG00000254444ENST00000529961.1 linkn.286+15727G>T intron_variant Intron 1 of 2 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 10, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.763G>T (p.V255F) alteration is located in exon 1 (coding exon 1) of the OR52B2 gene. This alteration results from a G to T substitution at nucleotide position 763, causing the valine (V) at amino acid position 255 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
0.10
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.016
T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.069
N
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.14
Sift
Benign
0.093
T
Sift4G
Benign
0.073
T
Polyphen
0.0
B
Vest4
0.20
MutPred
0.50
Loss of catalytic residue at V255 (P = 0.0606);
MVP
0.54
MPC
0.038
ClinPred
0.11
T
GERP RS
3.2
Varity_R
0.19
gMVP
0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-6190794; API