11-4545374-T-C

Variant summary

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

The NM_001004137.1(OR52M1):ā€‹c.184T>Cā€‹(p.Tyr62His) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

OR52M1
NM_001004137.1 missense

Scores

8
3
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.65
Variant links:
Genes affected
OR52M1 (HGNC:15225): (olfactory receptor family 52 subfamily M 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR52M1NM_001004137.1 linkuse as main transcriptc.184T>C p.Tyr62His missense_variant 1/1 ENST00000360213.1 NP_001004137.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR52M1ENST00000360213.1 linkuse as main transcriptc.184T>C p.Tyr62His missense_variant 1/1 NM_001004137.1 ENSP00000353343 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
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
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251246
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135788
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000198
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.0000103
AC:
15
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000306
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000264

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 06, 2021The c.184T>C (p.Y62H) alteration is located in exon 1 (coding exon 1) of the OR52M1 gene. This alteration results from a T to C substitution at nucleotide position 184, causing the tyrosine (Y) at amino acid position 62 to be replaced by a histidine (H). 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
Pathogenic
0.58
BayesDel_addAF
Benign
-0.068
T
BayesDel_noAF
Benign
-0.34
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.021
T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.72
D
MetaSVM
Benign
-0.61
T
MutationAssessor
Pathogenic
3.2
M
MutationTaster
Benign
0.99
D
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-4.4
D
REVEL
Uncertain
0.34
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.68
MutPred
0.47
Loss of catalytic residue at Y62 (P = 0.0669);
MVP
0.65
ClinPred
0.99
D
GERP RS
4.8
Varity_R
0.72
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1405956385; hg19: chr11-4566604; API