11-55820134-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001001952.1(OR5D18):​c.505T>A​(p.Phe169Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,613,950 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00085 ( 2 hom., cov: 31)
Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

OR5D18
NM_001001952.1 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13046214).
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR5D18NM_001001952.1 linkuse as main transcriptc.505T>A p.Phe169Ile missense_variant 1/1 ENST00000333976.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR5D18ENST00000333976.7 linkuse as main transcriptc.505T>A p.Phe169Ile missense_variant 1/1 NM_001001952.1 P1

Frequencies

GnomAD3 genomes
AF:
0.000856
AC:
130
AN:
151958
Hom.:
2
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000363
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000852
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00146
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000851
AC:
214
AN:
251448
Hom.:
1
AF XY:
0.000935
AC XY:
127
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.000616
Gnomad AMR exome
AF:
0.000752
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000915
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.00125
Gnomad OTH exome
AF:
0.000651
GnomAD4 exome
AF:
0.00153
AC:
2236
AN:
1461874
Hom.:
3
Cov.:
36
AF XY:
0.00157
AC XY:
1140
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.000783
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00112
Gnomad4 FIN exome
AF:
0.000112
Gnomad4 NFE exome
AF:
0.00179
Gnomad4 OTH exome
AF:
0.00141
GnomAD4 genome
AF:
0.000848
AC:
129
AN:
152076
Hom.:
2
Cov.:
31
AF XY:
0.000753
AC XY:
56
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.000362
Gnomad4 AMR
AF:
0.000785
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00146
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00112
Hom.:
0
Bravo
AF:
0.000952
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.00285
AC:
11
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000815
AC:
7
ExAC
AF:
0.000865
AC:
105
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00169
EpiControl
AF:
0.00154

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 08, 2022The c.505T>A (p.F169I) alteration is located in exon 1 (coding exon 1) of the OR5D18 gene. This alteration results from a T to A substitution at nucleotide position 505, causing the phenylalanine (F) at amino acid position 169 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
0.18
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T
Eigen
Uncertain
0.36
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.1
M
MutationTaster
Benign
0.56
D
PrimateAI
Benign
0.30
T
PROVEAN
Pathogenic
-5.1
D
REVEL
Benign
0.16
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.46
MVP
0.61
MPC
0.38
ClinPred
0.074
T
GERP RS
4.8
Varity_R
0.59
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs141630065; hg19: chr11-55587610; API