chr11-4489046-T-C

Variant summary

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

The NM_001005171.3(OR52K1):ā€‹c.146T>Cā€‹(p.Phe49Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

OR52K1
NM_001005171.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.117
Variant links:
Genes affected
OR52K1 (HGNC:15222): (olfactory receptor family 52 subfamily K 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12411472).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR52K1NM_001005171.3 linkuse as main transcriptc.146T>C p.Phe49Ser missense_variant 2/2 ENST00000641528.1 NP_001005171.2
OR52K1NM_001385736.1 linkuse as main transcriptc.107T>C p.Phe36Ser missense_variant 2/2 NP_001372665.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR52K1ENST00000641528.1 linkuse as main transcriptc.146T>C p.Phe49Ser missense_variant 2/2 NM_001005171.3 ENSP00000493011 P1
ENST00000690302.1 linkuse as main transcriptn.380-30617T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
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
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251396
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461852
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

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 GeneticsMar 29, 2022The c.146T>C (p.F49S) alteration is located in exon 1 (coding exon 1) of the OR52K1 gene. This alteration results from a T to C substitution at nucleotide position 146, causing the phenylalanine (F) at amino acid position 49 to be replaced by a serine (S). 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
0.19
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
12
DANN
Benign
0.91
DEOGEN2
Benign
0.014
T;.;T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.022
.;T;T
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.3
L;.;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-3.4
.;.;D
REVEL
Benign
0.064
Sift
Benign
0.086
.;.;T
Sift4G
Benign
0.13
.;.;T
Polyphen
0.90
P;.;P
Vest4
0.44
MVP
0.21
ClinPred
0.31
T
GERP RS
2.4
Varity_R
0.19
gMVP
0.20

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.

Other links and lift over

dbSNP: rs146030293; hg19: chr11-4510276; API