14-20117690-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004715.5(OR4K17):​c.191G>A​(p.Gly64Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

OR4K17
NM_001004715.5 missense

Scores

1
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.03
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09663966).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR4K17NM_001004715.5 linkuse as main transcriptc.191G>A p.Gly64Asp missense_variant 2/2 ENST00000641386.2 NP_001004715.3 A0A126GVZ4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR4K17ENST00000641386.2 linkuse as main transcriptc.191G>A p.Gly64Asp missense_variant 2/2 NM_001004715.5 ENSP00000493449.2 Q8NGC6
OR4K17ENST00000641633.2 linkuse as main transcriptc.191G>A p.Gly64Asp missense_variant 3/3 ENSP00000493115.2 Q8NGC6

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151874
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151874
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74144
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
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:
0.00
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsApr 04, 2024The c.284G>A (p.G95D) 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 284, causing the glycine (G) at amino acid position 95 to be replaced by an aspartic acid (D). 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
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
15
DANN
Benign
0.97
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.19
.;.;T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.097
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.21
T
PROVEAN
Uncertain
-2.8
.;.;D
REVEL
Benign
0.12
Sift
Uncertain
0.0080
.;.;D
Sift4G
Pathogenic
0.0010
.;.;D
Vest4
0.22
MVP
0.10
MPC
.;.;9.22648080292E-4
ClinPred
0.21
T
GERP RS
0.58
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs201880365; hg19: chr14-20585849; API