14-19748019-G-T

Variant summary

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

The NM_001405963.1(OR4Q3):​c.616G>T​(p.Val206Leu) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 36)

Consequence

OR4Q3
NM_001405963.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.342
Variant links:
Genes affected
OR4Q3 (HGNC:15426): (olfactory receptor family 4 subfamily Q member 3) 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]
OR4N2 (HGNC:14742): (olfactory receptor family 4 subfamily N 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 seven-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, Mar 2014]

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=0.015634477).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR4Q3NM_001405963.1 linkuse as main transcriptc.616G>T p.Val206Leu missense_variant 2/2 NP_001392892.1
OR4Q3NM_172194.1 linkuse as main transcriptc.592G>T p.Val198Leu missense_variant 1/1 NP_751944.1 Q8NH05A0A126GW32
OR4Q3XM_024449618.1 linkuse as main transcriptc.781G>T p.Val261Leu missense_variant 3/4 XP_024305386.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR4Q3ENST00000642117.2 linkuse as main transcriptc.616G>T p.Val206Leu missense_variant 2/2 ENSP00000492928.2 A0A2U3TZU4
OR4N2ENST00000557414.1 linkuse as main transcriptc.-303-13869G>T intron_variant 6 ENSP00000451462.1 G3V3W5

Frequencies

GnomAD3 genomes
Cov.:
36
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
36

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 GeneticsJun 17, 2024The c.592G>T (p.V198L) alteration is located in exon 1 (coding exon 1) of the OR4Q3 gene. This alteration results from a G to T substitution at nucleotide position 592, causing the valine (V) at amino acid position 198 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
0.10
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
6.5
DANN
Benign
0.47
DEOGEN2
Benign
0.0050
.;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.60
T;T
M_CAP
Benign
0.00089
T
MetaRNN
Benign
0.016
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-1.6
.;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.31
.;N
REVEL
Benign
0.011
Sift
Benign
1.0
.;T
Sift4G
Benign
1.0
.;T
Polyphen
0.0040
.;B
Vest4
0.082
MutPred
0.28
.;Loss of catalytic residue at V198 (P = 0.1152);
MVP
0.10
ClinPred
0.065
T
GERP RS
-1.4
Varity_R
0.037
gMVP
0.091

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: chr14-20216178; API