Genetic Variant NM_001005495.1:c.152T>A (chr1-248473502-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001005495.1(OR2T3):c.152T>A(p.Ile51Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,525,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

OR2T3
NM_001005495.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

OR2T3 (HGNC:14727): (olfactory receptor family 2 subfamily T 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]

OR2T3 links:

LOC105373279 (HGNC:):

LOC105373279 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T3	NM_001005495.1 link	c.152T>A	p.Ile51Asn	missense_variant	Exon 1 of 1	ENST00000359594.3	NP_001005495.1	Q8NH03A0A126GVW5
LOC105373279	XR_007067006.1 link	n.136-3343A>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2T3	ENST00000359594.3 link	c.152T>A	p.Ile51Asn	missense_variant	Exon 1 of 1	6	NM_001005495.1	ENSP00000352604.2		Q8NH03

Frequencies

GnomAD3 genomes

AF:

0.000310

AC:

AN:

144960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000861

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000496

Gnomad ASJ

AF:

0.000299

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

220382

Hom.:

AF XY:

0.000143

AC XY:

AN XY:

118596

show subpopulations

Gnomad AFR exome

AF:

0.000482

Gnomad AMR exome

AF:

0.000341

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:

0.000136

Gnomad OTH exome

AF:

0.000940

GnomAD4 exome

AF:

0.000110

AC:

152

AN:

1380606

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

688820

show subpopulations

Gnomad4 AFR exome

AF:

0.000751

Gnomad4 AMR exome

AF:

0.000342

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000721

Gnomad4 OTH exome

AF:

0.000486

GnomAD4 genome

AF:

0.000310

AC:

AN:

145070

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

AN XY:

70384

show subpopulations

Gnomad4 AFR

AF:

0.000858

Gnomad4 AMR

AF:

0.000495

Gnomad4 ASJ

AF:

0.000299

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000303

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000288

Hom.:

ESP6500AA

AF:

0.000695

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000125

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.152T>A (p.I51N) alteration is located in exon 1 (coding exon 1) of the OR2T3 gene. This alteration results from a T to A substitution at nucleotide position 152, causing the isoleucine (I) at amino acid position 51 to be replaced by an asparagine (N). 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

-0.33

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

0.016

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.11

M_CAP

Benign

0.00098

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.7

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.030

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.58

MVP

0.63

ClinPred

0.38

GERP RS

2.6

Varity_R

0.46

gMVP

0.30

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