14-20117830-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001004715.5(OR4K17):​c.331G>A​(p.Glu111Lys) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

OR4K17
NM_001004715.5 missense

Scores

5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54
Variant links:
Genes affected
OR4K17 (HGNC:15355): (olfactory receptor family 4 subfamily K 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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27141416).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR4K17NM_001004715.5 linkuse as main transcriptc.331G>A p.Glu111Lys missense_variant 2/2 ENST00000641386.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR4K17ENST00000641386.2 linkuse as main transcriptc.331G>A p.Glu111Lys missense_variant 2/2 NM_001004715.5 P1
OR4K17ENST00000641633.2 linkuse as main transcriptc.331G>A p.Glu111Lys missense_variant 3/3 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31

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 GeneticsJul 26, 2022The c.424G>A (p.E142K) alteration is located in exon 1 (coding exon 1) of the OR4K17 gene. This alteration results from a G to A substitution at nucleotide position 424, causing the glutamic acid (E) at amino acid position 142 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
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
23
DANN
Uncertain
1.0
Eigen
Benign
0.055
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.57
D
LIST_S2
Uncertain
0.91
.;.;D
M_CAP
Benign
0.00067
T
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.95
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-3.9
.;.;D
REVEL
Benign
0.094
Sift
Uncertain
0.0030
.;.;D
Sift4G
Uncertain
0.010
.;.;D
Vest4
0.50
MVP
0.13
MPC
0.0019
ClinPred
0.82
D
GERP RS
0.88
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr14-20585989; COSMIC: COSV105876917; API