chr14-19876700-G-T

Variant summary

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

The NM_001005501.2(OR4K2):​c.433G>T​(p.Val145Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,834 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: not found (cov: 35)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

OR4K2
NM_001005501.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.724
Variant links:
Genes affected
OR4K2 (HGNC:14728): (olfactory receptor family 4 subfamily K 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]

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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=0.09203932).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR4K2NM_001005501.2 linkuse as main transcriptc.433G>T p.Val145Leu missense_variant 2/2 ENST00000641885.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR4K2ENST00000641885.1 linkuse as main transcriptc.433G>T p.Val145Leu missense_variant 2/2 NM_001005501.2 P1
OR4K2ENST00000298642.2 linkuse as main transcriptc.433G>T p.Val145Leu missense_variant 1/1 P1
OR4K2ENST00000641522.1 linkuse as main transcriptn.1133+316G>T intron_variant, non_coding_transcript_variant
OR4K2ENST00000641785.1 linkuse as main transcriptn.1133+316G>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251196
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135734
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461834
Hom.:
0
Cov.:
36
AF XY:
0.00000413
AC XY:
3
AN XY:
727220
show subpopulations
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:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
35
ExAC
AF:
0.00000824
AC:
1

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 GeneticsFeb 15, 2023The c.433G>T (p.V145L) alteration is located in exon 1 (coding exon 1) of the OR4K2 gene. This alteration results from a G to T substitution at nucleotide position 433, causing the valine (V) at amino acid position 145 to be replaced by a leucine (L). 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
0.22
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
14
DANN
Benign
0.97
DEOGEN2
Benign
0.0050
T;T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.20
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.29
.;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.092
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.1
L;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-2.0
.;N
REVEL
Benign
0.11
Sift
Benign
0.26
.;T
Sift4G
Benign
0.48
.;T
Polyphen
0.043
B;B
Vest4
0.080
MutPred
0.42
Loss of catalytic residue at V145 (P = 0.0261);Loss of catalytic residue at V145 (P = 0.0261);
MVP
0.46
MPC
.;5.81669046081E-4
ClinPred
0.34
T
GERP RS
4.2
Varity_R
0.12
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs374716082; hg19: chr14-20344859; COSMIC: COSV100064350; API