chr1-248061435-G-A

Position:

chr1-248061435-G-A

Variant summary

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

The NM_001004687.2(OR2L3):c.754G>A(p.Ala252Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,906 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: 𝑓 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

OR2L3
NM_001004687.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.217

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 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=0.049838305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2L3	NM_001004687.2 linkuse as main transcript	c.754G>A	p.Ala252Thr	missense_variant	2/2	ENST00000359959.4
LOC105373275	XR_949369.3 linkuse as main transcript	n.418+3701C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
OR2L3	ENST00000359959.4 linkuse as main transcript	c.754G>A	p.Ala252Thr	missense_variant	2/2	NM_001004687.2	P1
OR2L3	ENST00000641161.1 linkuse as main transcript	c.754G>A	p.Ala252Thr	missense_variant	2/2		P1
OR2L3	ENST00000641649.1 linkuse as main transcript	c.754G>A	p.Ala252Thr	missense_variant	3/3		P1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251392

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000588

Gnomad4 OTH

AF:

0.00

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

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

Dec 15, 2022

The c.754G>A (p.A252T) alteration is located in exon 1 (coding exon 1) of the OR2L3 gene. This alteration results from a G to A substitution at nucleotide position 754, causing the alanine (A) at amino acid position 252 to be replaced by a threonine (T). 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

0.091

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.5

DANN

Benign

0.93

DEOGEN2

Benign

0.012

T;T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.67

.;.;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.23

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-2.2

N;.;.

REVEL

Benign

0.052

Sift

Benign

0.049

D;.;.

Sift4G

Uncertain

0.0070

D;.;.

Polyphen

0.048

B;B;B

Vest4

0.097

MutPred

0.54

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.29

MPC

0.18

ClinPred

0.071

GERP RS

2.0

Varity_R

0.099

gMVP

0.055

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

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