Variant 1-248650085-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001001824.2(OR2T27):c.800C>G(p.Thr267Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,573,184 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 4 hom., cov: 26)

Exomes 𝑓: 0.00031 ( 27 hom. )

Consequence

OR2T27
NM_001001824.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.383

Variant links:

Genes affected

OR2T27 (HGNC:31252): (olfactory receptor family 2 subfamily T member 27) 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]

OR2T27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T27	NM_001001824.2 link	c.800C>G	p.Thr267Ser	missense_variant	2/2	ENST00000460972.4	NP_001001824.1	Q8NH04
OR2T27	NM_001386060.1 link	c.800C>G	p.Thr267Ser	missense_variant	3/3		NP_001372989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T27	ENST00000460972.4 link	c.800C>G	p.Thr267Ser	missense_variant	2/2	6	NM_001001824.2	ENSP00000493412.1		Q8NH04
OR2T27	ENST00000641652.1 link	c.800C>G	p.Thr267Ser	missense_variant	3/3			ENSP00000493434.1		Q8NH04

Frequencies

GnomAD3 genomes

AF:

0.000353

AC:

AN:

144460

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000478

Gnomad ASJ

AF:

0.00850

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000182

Gnomad OTH

AF:

0.000998

GnomAD3 exomes

AF:

0.000294

AC:

AN:

245084

Hom.:

AF XY:

0.000249

AC XY:

AN XY:

132590

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.000178

Gnomad ASJ exome

AF:

0.00393

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.000832

GnomAD4 exome

AF:

0.000309

AC:

442

AN:

1428724

Hom.:

Cov.:

AF XY:

0.000277

AC XY:

197

AN XY:

711310

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.000434

Gnomad4 ASJ exome

AF:

0.00685

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.0000356

Gnomad4 FIN exome

AF:

0.0000388

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000726

GnomAD4 genome

AF:

0.000353

AC:

AN:

144460

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

70180

show subpopulations

Gnomad4 AFR

AF:

0.0000260

Gnomad4 AMR

AF:

0.000478

Gnomad4 ASJ

AF:

0.00850

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000182

Gnomad4 OTH

AF:

0.000998

Alfa

AF:

0.00120

Hom.:

ExAC

AF:

0.000450

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 06, 2022

The c.800C>G (p.T267S) alteration is located in exon 1 (coding exon 1) of the OR2T27 gene. This alteration results from a C to G substitution at nucleotide position 800, causing the threonine (T) at amino acid position 267 to be replaced by a serine (S). 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

0.094

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.29

DEOGEN2

Benign

0.0032

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.19

.;.;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0091

T;T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.1

.;.;N

REVEL

Benign

0.098

Sift

Benign

0.49

.;.;T

Sift4G

Benign

1.0

.;.;T

Polyphen

0.43

B;B;B

Vest4

0.092

MutPred

0.39

Gain of disorder (P = 0.0363);Gain of disorder (P = 0.0363);Gain of disorder (P = 0.0363);

MVP

0.27

MPC

0.53

ClinPred

0.069

GERP RS

2.5

Varity_R

0.10

gMVP

0.051

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.31

Position offset: -1

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