1-248061274-T-A

Position:

chr1-248061274-T-A

Variant summary

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

The NM_001004687.2(OR2L3):c.593T>A(p.Val198Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,605,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

OR2L3
NM_001004687.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0500

Variant links:

Genes affected

OR2L3 (HGNC:15009): (olfactory receptor family 2 subfamily L 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]

OR2L3 links:

LOC105373275 (HGNC:):

LOC105373275 links:

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=0.33162946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2L3	NM_001004687.2 linkuse as main transcript	c.593T>A	p.Val198Glu	missense_variant	2/2	ENST00000359959.4	NP_001004687.1
LOC105373275	XR_949369.3 linkuse as main transcript	n.418+3862A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	Appris
OR2L3	ENST00000359959.4 linkuse as main transcript	c.593T>A	p.Val198Glu	missense_variant	2/2	NM_001004687.2	ENSP00000353044	P1
OR2L3	ENST00000641161.1 linkuse as main transcript	c.593T>A	p.Val198Glu	missense_variant	2/2		ENSP00000493424	P1
OR2L3	ENST00000641649.1 linkuse as main transcript	c.593T>A	p.Val198Glu	missense_variant	3/3		ENSP00000493020	P1

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250800

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135590

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455828

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724568

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000542

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72832

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.593T>A (p.V198E) alteration is located in exon 1 (coding exon 1) of the OR2L3 gene. This alteration results from a T to A substitution at nucleotide position 593, causing the valine (V) at amino acid position 198 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0069

T;T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.035

LIST_S2

Uncertain

0.91

.;.;D

M_CAP

Benign

0.00064

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.3

M;M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

PROVEAN

Pathogenic

-5.0

D;.;.

REVEL

Benign

0.025

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0010

D;.;.

Polyphen

1.0

D;D;D

Vest4

0.44

MutPred

0.54

Loss of stability (P = 0.1427);Loss of stability (P = 0.1427);Loss of stability (P = 0.1427);

MVP

0.46

MPC

0.81

ClinPred

0.98

GERP RS

0.63

Varity_R

0.77

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over