Variant chr1-248473649-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001005495.1(OR2T3):c.299C>T(p.Ser100Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,611,682 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.000073 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

OR2T3
NM_001005495.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.69

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 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=0.04426399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T3	NM_001005495.1 linkuse as main transcript	c.299C>T	p.Ser100Leu	missense_variant	1/1	ENST00000359594.3	NP_001005495.1
LOC105373279	XR_007067006.1 linkuse as main transcript	n.136-3490G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T3	ENST00000359594.3 linkuse as main transcript	c.299C>T	p.Ser100Leu	missense_variant	1/1		NM_001005495.1	ENSP00000352604	P1

Frequencies

GnomAD3 genomes

AF:

0.0000731

AC:

AN:

150574

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

250654

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135444

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000795

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000112

AC:

163

AN:

1461108

Hom.:

Cov.:

AF XY:

0.0000935

AC XY:

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.000143

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000731

AC:

AN:

150574

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

73498

show subpopulations

Gnomad4 AFR

AF:

0.0000248

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:

0.000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000247

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 21, 2022

The c.299C>T (p.S100L) alteration is located in exon 1 (coding exon 1) of the OR2T3 gene. This alteration results from a C to T substitution at nucleotide position 299, causing the serine (S) at amino acid position 100 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

0.068

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.031

DANN

Benign

0.67

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0022

M_CAP

Benign

0.00050

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.43

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

0.24

REVEL

Benign

0.013

Sift

Benign

0.56

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.075

MutPred

0.39

Loss of disorder (P = 0.0073);

MVP

0.085

ClinPred

0.032

GERP RS

-3.7

Varity_R

0.015

gMVP

0.054

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