11-55913880-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001001960.1(OR5W2):​c.703T>A​(p.Phe235Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,550 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 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR5W2
NM_001001960.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.866
Variant links:
Genes affected
OR5W2 (HGNC:15299): (olfactory receptor family 5 subfamily W member 2) 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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05272016).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR5W2NM_001001960.1 linkc.703T>A p.Phe235Ile missense_variant Exon 1 of 1 ENST00000344514.1 NP_001001960.1 Q8NH69

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR5W2ENST00000344514.1 linkc.703T>A p.Phe235Ile missense_variant Exon 1 of 1 6 NM_001001960.1 ENSP00000342448.1 Q8NH69

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151904
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.000958
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250794
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135582
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461646
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151904
Hom.:
0
Cov.:
33
AF XY:
0.0000270
AC XY:
2
AN XY:
74186
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
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:
0.000958
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.0000756
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 02, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.703T>A (p.F235I) alteration is located in exon 1 (coding exon 1) of the OR5W2 gene. This alteration results from a T to A substitution at nucleotide position 703, causing the phenylalanine (F) at amino acid position 235 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
0.093
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
9.7
DANN
Benign
0.85
DEOGEN2
Benign
0.0043
T
Eigen
Benign
-0.94
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.17
T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.053
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.20
N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.053
Sift
Benign
0.39
T
Sift4G
Benign
0.36
T
Polyphen
0.012
B
Vest4
0.27
MutPred
0.21
Loss of methylation at R234 (P = 0.0741);
MVP
0.11
MPC
0.0027
ClinPred
0.036
T
GERP RS
-0.090
Varity_R
0.22
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs762844343; hg19: chr11-55681356; API