NM_001004744.1:c.494G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001004744.1(OR8U3):​c.494G>A​(p.Arg165His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

OR8U3
NM_001004744.1 missense

Scores

15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.40
Variant links:
Genes affected
OR8U3 (HGNC:14841): (olfactory receptor family 8 subfamily U member 3) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.014554709).
BP6
Variant 11-56417739-C-T is Benign according to our data. Variant chr11-56417739-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3412313.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR8U3NM_001004744.1 linkc.494G>A p.Arg165His missense_variant Exon 1 of 1 ENST00000623286.1 NP_001004744.1 Q8NH85

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR8U3ENST00000623286.1 linkc.494G>A p.Arg165His missense_variant Exon 1 of 1 6 NM_001004744.1 ENSP00000485324.1 Q8NH85

Frequencies

GnomAD3 genomes
AF:
0.000322
AC:
49
AN:
151956
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000870
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.000960
GnomAD3 exomes
AF:
0.000132
AC:
33
AN:
250926
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135588
show subpopulations
Gnomad AFR exome
AF:
0.00111
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000105
AC:
153
AN:
1461786
Hom.:
0
Cov.:
39
AF XY:
0.000107
AC XY:
78
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.00117
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000773
Gnomad4 OTH exome
AF:
0.000248
GnomAD4 genome
AF:
0.000322
AC:
49
AN:
152074
Hom.:
0
Cov.:
32
AF XY:
0.000296
AC XY:
22
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.000868
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.000950
Alfa
AF:
0.000170
Hom.:
0
Bravo
AF:
0.000314
ESP6500AA
AF:
0.000909
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000107
AC:
13
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jul 23, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.88
DANN
Benign
0.70
DEOGEN2
Benign
0.0052
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.18
T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.015
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.99
L
PrimateAI
Benign
0.18
T
Polyphen
0.013
B
ClinPred
0.012
T
GERP RS
-7.0
Varity_R
0.021
gMVP
0.050

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs138983419; hg19: chr11-56185215; COSMIC: COSV56571407; COSMIC: COSV56571407; API