14-19975953-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001005486.2(OR4K15):​c.363C>A​(p.Asp121Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

OR4K15
NM_001005486.2 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.208
Variant links:
Genes affected
OR4K15 (HGNC:15353): (olfactory receptor family 4 subfamily K member 15) 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR4K15NM_001005486.2 linkc.363C>A p.Asp121Glu missense_variant Exon 1 of 1 ENST00000305051.6 NP_001005486.2 Q8NH41

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR4K15ENST00000305051.6 linkc.363C>A p.Asp121Glu missense_variant Exon 1 of 1 6 NM_001005486.2 ENSP00000304077.5 Q8NH41

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
37
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
Feb 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.435C>A (p.D145E) alteration is located in exon 1 (coding exon 1) of the OR4K15 gene. This alteration results from a C to A substitution at nucleotide position 435, causing the aspartic acid (D) at amino acid position 145 to be replaced by a glutamic acid (E). 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
Pathogenic
0.61
BayesDel_addAF
Uncertain
0.037
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.074
.;T
Eigen
Uncertain
0.41
Eigen_PC
Benign
0.16
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.0025
T
MetaRNN
Uncertain
0.48
T;T
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Pathogenic
3.6
.;H
PrimateAI
Benign
0.26
T
PROVEAN
Uncertain
-3.9
.;D
REVEL
Benign
0.23
Sift
Pathogenic
0.0
.;D
Sift4G
Pathogenic
0.0
.;D
Polyphen
1.0
.;D
Vest4
0.77
MutPred
0.65
.;Gain of catalytic residue at V148 (P = 2e-04);
MVP
0.57
MPC
0.28
ClinPred
0.99
D
GERP RS
1.9
Varity_R
0.95
gMVP
0.47

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: chr14-20444112; API