Variant chr1-248272882-G-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_001004695.2(OR2T33):c.933C>G(p.His311Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000788 in 1,613,520 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 2 hom. )

Consequence

OR2T33
NM_001004695.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.03

Variant links:

Genes affected

OR2T33 (HGNC:31255): (olfactory receptor family 2 subfamily T member 33) 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]

OR2T33 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014689386).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T33	NM_001004695.2 linkuse as main transcript	c.933C>G	p.His311Gln	missense_variant	2/2	ENST00000641220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T33	ENST00000641220.1 linkuse as main transcript	c.933C>G	p.His311Gln	missense_variant	2/2		NM_001004695.2	P1
OR2T33	ENST00000318021.4 linkuse as main transcript	c.933C>G	p.His311Gln	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.000487

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000755

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000423

AC:

106

AN:

250556

Hom.:

AF XY:

0.000384

AC XY:

AN XY:

135326

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000795

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000820

AC:

1198

AN:

1461308

Hom.:

Cov.:

AF XY:

0.000797

AC XY:

579

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.000486

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000755

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000580

Hom.:

Bravo

AF:

0.000397

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000534

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

Jul 14, 2021

The c.933C>G (p.H311Q) alteration is located in exon 1 (coding exon 1) of the OR2T33 gene. This alteration results from a C to G substitution at nucleotide position 933, causing the histidine (H) at amino acid position 311 to be replaced by a glutamine (Q). 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

0.086

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.042

DANN

Benign

0.29

DEOGEN2

Benign

0.0015

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00075

LIST_S2

Benign

0.16

.;T

M_CAP

Benign

0.00070

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

.;N

REVEL

Benign

0.012

Sift

Benign

0.60

.;T

Sift4G

Benign

0.10

.;T

Polyphen

0.0

B;B

Vest4

0.071

MutPred

0.25

Gain of MoRF binding (P = 0.0832);Gain of MoRF binding (P = 0.0832);

MVP

0.16

MPC

1.1

ClinPred

0.034

GERP RS

-3.1

Varity_R

0.038

gMVP

0.032

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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