11-55820316-G-T

Variant summary

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

The NM_001001952.1(OR5D18):​c.687G>T​(p.Met229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,520 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 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OR5D18
NM_001001952.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.711
Variant links:
Genes affected
OR5D18 (HGNC:15285): (olfactory receptor family 5 subfamily D member 18) 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=0.07861498).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR5D18NM_001001952.1 linkuse as main transcriptc.687G>T p.Met229Ile missense_variant 1/1 ENST00000333976.7 NP_001001952.1 Q8NGL1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR5D18ENST00000333976.7 linkuse as main transcriptc.687G>T p.Met229Ile missense_variant 1/16 NM_001001952.1 ENSP00000335025.4 Q8NGL1

Frequencies

GnomAD3 genomes
AF:
0.0000396
AC:
6
AN:
151644
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000146
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
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461876
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000396
AC:
6
AN:
151644
Hom.:
0
Cov.:
32
AF XY:
0.0000405
AC XY:
3
AN XY:
74030
show subpopulations
Gnomad4 AFR
AF:
0.000146
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
Bravo
AF:
0.00000756

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 GeneticsFeb 12, 2024The c.687G>T (p.M229I) alteration is located in exon 1 (coding exon 1) of the OR5D18 gene. This alteration results from a G to T substitution at nucleotide position 687, causing the methionine (M) at amino acid position 229 to be replaced by an isoleucine (I). 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
0.24
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
9.9
DANN
Benign
0.30
DEOGEN2
Benign
0.0052
T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.079
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.95
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.11
Sift
Benign
0.80
T
Sift4G
Benign
1.0
T
Polyphen
0.0080
B
Vest4
0.18
MutPred
0.62
Gain of methylation at K228 (P = 0.027);
MVP
0.19
MPC
0.053
ClinPred
0.059
T
GERP RS
3.8
Varity_R
0.12
gMVP
0.14

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: rs1453028770; hg19: chr11-55587792; API