11-4882294-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001004759.3(OR51T1):ā€‹c.395T>Gā€‹(p.Leu132Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

OR51T1
NM_001004759.3 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27
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_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR51T1NM_001004759.3 linkuse as main transcriptc.395T>G p.Leu132Arg missense_variant 1/1 ENST00000322049.1 NP_001004759.2 Q8NGJ9A0A0C4DFX5
MMP26NM_021801.5 linkuse as main transcriptc.-144-105774T>G intron_variant ENST00000380390.6 NP_068573.2 Q9NRE1
MMP26NM_001384608.1 linkuse as main transcriptc.-152-105976T>G intron_variant NP_001371537.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR51T1ENST00000322049.1 linkuse as main transcriptc.395T>G p.Leu132Arg missense_variant 1/16 NM_001004759.3 ENSP00000322679.1 Q8NGJ9
MMP26ENST00000380390.6 linkuse as main transcriptc.-144-105774T>G intron_variant 5 NM_021801.5 ENSP00000369753.1 Q9NRE1
MMP26ENST00000300762.2 linkuse as main transcriptc.-152-105976T>G intron_variant 1 ENSP00000300762.2 A0A8J8YUH5
OR51T1ENST00000380378.1 linkuse as main transcriptc.476T>G p.Leu159Arg missense_variant 1/16 ENSP00000369738.1 A0A0C4DFX5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250502
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135354
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461756
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 30, 2024The c.476T>G (p.L159R) alteration is located in exon 1 (coding exon 1) of the OR51T1 gene. This alteration results from a T to G substitution at nucleotide position 476, causing the leucine (L) at amino acid position 159 to be replaced by an arginine (R). 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
0.26
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
.;T
Eigen
Pathogenic
0.74
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.045
D
MetaRNN
Pathogenic
0.95
D;D
MetaSVM
Benign
-0.35
T
MutationAssessor
Pathogenic
4.7
.;H
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-6.0
D;D
REVEL
Uncertain
0.44
Sift
Uncertain
0.0020
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.93
MutPred
0.71
.;Gain of methylation at L132 (P = 0.0236);
MVP
0.47
MPC
0.27
ClinPred
0.91
D
GERP RS
4.5
Varity_R
0.84
gMVP
0.61

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: rs1429589197; hg19: chr11-4903524; API