chr11-58358160-C-T

Variant summary

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

The NM_001005489.2(OR5B17):​c.910G>A​(p.Glu304Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OR5B17
NM_001005489.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.958
Variant links:
Genes affected
OR5B17 (HGNC:15267): (olfactory receptor family 5 subfamily B member 17) 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=0.061850965).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR5B17NM_001005489.2 linkuse as main transcriptc.910G>A p.Glu304Lys missense_variant 1/1 ENST00000357377.3 NP_001005489.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR5B17ENST00000357377.3 linkuse as main transcriptc.910G>A p.Glu304Lys missense_variant 1/1 NM_001005489.2 ENSP00000349945 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1447310
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
718486
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:
0.00
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 GeneticsMay 16, 2024The c.910G>A (p.E304K) alteration is located in exon 1 (coding exon 1) of the OR5B17 gene. This alteration results from a G to A substitution at nucleotide position 910, causing the glutamic acid (E) at amino acid position 304 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
0.080
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
1.2
DANN
Benign
0.79
DEOGEN2
Benign
0.0023
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0072
N
LIST_S2
Benign
0.13
T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.062
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.70
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.74
N
REVEL
Benign
0.024
Sift
Benign
0.58
T
Sift4G
Benign
0.64
T
Polyphen
0.0
B
Vest4
0.17
MutPred
0.34
Gain of MoRF binding (P = 4e-04);
MVP
0.21
MPC
0.0054
ClinPred
0.040
T
GERP RS
1.6
Varity_R
0.11
gMVP
0.048

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-58125633; COSMIC: COSV62160206; COSMIC: COSV62160206; API