11-4882573-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004759.3(OR51T1):​c.674G>A​(p.Arg225His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

OR51T1
NM_001004759.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.606
Variant links:
Genes affected
OR51T1 (HGNC:15205): (olfactory receptor family 51 subfamily T 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]
MMP26 (HGNC:14249): (matrix metallopeptidase 26) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.054029435).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR51T1NM_001004759.3 linkuse as main transcriptc.674G>A p.Arg225His missense_variant 1/1 ENST00000322049.1 NP_001004759.2 Q8NGJ9A0A0C4DFX5
MMP26NM_021801.5 linkuse as main transcriptc.-144-105495G>A intron_variant ENST00000380390.6 NP_068573.2 Q9NRE1
MMP26NM_001384608.1 linkuse as main transcriptc.-152-105697G>A intron_variant NP_001371537.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR51T1ENST00000322049.1 linkuse as main transcriptc.674G>A p.Arg225His missense_variant 1/16 NM_001004759.3 ENSP00000322679.1 Q8NGJ9
MMP26ENST00000380390.6 linkuse as main transcriptc.-144-105495G>A intron_variant 5 NM_021801.5 ENSP00000369753.1 Q9NRE1
MMP26ENST00000300762.2 linkuse as main transcriptc.-152-105697G>A intron_variant 1 ENSP00000300762.2 A0A8J8YUH5
OR51T1ENST00000380378.1 linkuse as main transcriptc.755G>A p.Arg252His missense_variant 1/16 ENSP00000369738.1 A0A0C4DFX5

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152002
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000139
AC:
35
AN:
251056
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
135684
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000247
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000161
AC:
235
AN:
1461660
Hom.:
0
Cov.:
32
AF XY:
0.000158
AC XY:
115
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000193
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000177
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000139
Hom.:
0
Bravo
AF:
0.000125
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000181
AC:
22
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000474

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 GeneticsApr 28, 2023The c.755G>A (p.R252H) alteration is located in exon 1 (coding exon 1) of the OR51T1 gene. This alteration results from a G to A substitution at nucleotide position 755, causing the arginine (R) at amino acid position 252 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
Benign
0.091
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
18
DANN
Benign
0.95
DEOGEN2
Benign
0.023
.;T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.69
T;T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.054
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.68
.;N
PrimateAI
Benign
0.17
T
PROVEAN
Benign
-0.84
N;N
REVEL
Benign
0.075
Sift
Benign
0.35
T;T
Sift4G
Benign
0.50
T;T
Polyphen
0.13
.;B
Vest4
0.34
MVP
0.26
MPC
0.050
ClinPred
0.027
T
GERP RS
3.1
Varity_R
0.031
gMVP
0.22

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: rs144368286; hg19: chr11-4903803; COSMIC: COSV59025074; COSMIC: COSV59025074; API