chr11-4848614-C-T

Variant summary

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

The NM_001004758.1(OR51S1):​c.595G>A​(p.Glu199Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 1,456,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

OR51S1
NM_001004758.1 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.172
Variant links:
Genes affected
OR51S1 (HGNC:15204): (olfactory receptor family 51 subfamily S 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]

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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=0.08640942).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR51S1NM_001004758.1 linkuse as main transcriptc.595G>A p.Glu199Lys missense_variant 1/1 ENST00000322101.5
MMP26NM_021801.5 linkuse as main transcriptc.-145+81273C>T intron_variant ENST00000380390.6
MMP26NM_001384608.1 linkuse as main transcriptc.-153+81273C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR51S1ENST00000322101.5 linkuse as main transcriptc.595G>A p.Glu199Lys missense_variant 1/1 NM_001004758.1 P1
MMP26ENST00000380390.6 linkuse as main transcriptc.-145+81273C>T intron_variant 5 NM_021801.5 P1
MMP26ENST00000300762.2 linkuse as main transcriptc.-153+81273C>T intron_variant 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000819
AC:
2
AN:
244342
Hom.:
0
AF XY:
0.0000152
AC XY:
2
AN XY:
131860
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000181
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000687
AC:
10
AN:
1456164
Hom.:
0
Cov.:
53
AF XY:
0.00000553
AC XY:
4
AN XY:
723848
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000901
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 10, 2023The c.595G>A (p.E199K) alteration is located in exon 1 (coding exon 1) of the OR51S1 gene. This alteration results from a G to A substitution at nucleotide position 595, causing the glutamic acid (E) at amino acid position 199 to be replaced by a lysine (K). 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
-0.22
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0025
T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.086
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.93
L
MutationTaster
Benign
0.97
D;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.055
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0070
D
Polyphen
0.081
B
Vest4
0.11
MutPred
0.55
Gain of ubiquitination at E199 (P = 0.0337);
MVP
0.43
MPC
0.0076
ClinPred
0.68
D
GERP RS
3.3
Varity_R
0.29
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs1439269302; hg19: chr11-4869844; COSMIC: COSV59057216; API