Variant chr1-248473580-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001005495.1(OR2T3):c.230T>C(p.Met77Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,574,100 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 1 hom., cov: 26)

Exomes 𝑓: 0.00025 ( 7 hom. )

Consequence

OR2T3
NM_001005495.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.736

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013682306).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T3	NM_001005495.1 linkuse as main transcript	c.230T>C	p.Met77Thr	missense_variant	1/1	ENST00000359594.3
LOC105373279	XR_007067006.1 linkuse as main transcript	n.136-3421A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T3	ENST00000359594.3 linkuse as main transcript	c.230T>C	p.Met77Thr	missense_variant	1/1		NM_001005495.1	P1

Frequencies

GnomAD3 genomes

AF:

0.000202

AC:

AN:

148460

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000204

Gnomad ASJ

AF:

0.00117

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00178

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0131

Gnomad NFE

AF:

0.000119

Gnomad OTH

AF:

0.000496

GnomAD3 exomes

AF:

0.000470

AC:

106

AN:

225622

Hom.:

AF XY:

0.000567

AC XY:

AN XY:

121608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000554

Gnomad ASJ exome

AF:

0.00141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000366

Gnomad OTH exome

AF:

0.00144

GnomAD4 exome

AF:

0.000249

AC:

355

AN:

1425536

Hom.:

Cov.:

AF XY:

0.000308

AC XY:

219

AN XY:

710982

show subpopulations

Gnomad4 AFR exome

AF:

0.000312

Gnomad4 AMR exome

AF:

0.000449

Gnomad4 ASJ exome

AF:

0.00120

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00115

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.000473

GnomAD4 genome

AF:

0.000209

AC:

AN:

148564

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

AN XY:

72348

show subpopulations

Gnomad4 AFR

AF:

0.0000498

Gnomad4 AMR

AF:

0.000203

Gnomad4 ASJ

AF:

0.00117

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00201

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000119

Gnomad4 OTH

AF:

0.000491

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000242

ExAC

AF:

0.000431

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

Mar 19, 2024

The c.230T>C (p.M77T) alteration is located in exon 1 (coding exon 1) of the OR2T3 gene. This alteration results from a T to C substitution at nucleotide position 230, causing the methionine (M) at amino acid position 77 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

0.11

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.8

DANN

Benign

0.40

DEOGEN2

Benign

0.0088

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.028

M_CAP

Benign

0.00040

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.45

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.041

Sift

Benign

0.039

Sift4G

Benign

0.27

Polyphen

0.017

Vest4

0.087

MVP

0.23

ClinPred

0.022

GERP RS

-1.3

Varity_R

0.093

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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