Variant 1-248592840-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001004693.2(OR2T10):c.929C>T(p.Pro310Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000288 in 1,526,346 control chromosomes in the GnomAD database, including 4 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 0.0000070 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000031 ( 4 hom. )

Consequence

OR2T10
NM_001004693.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.214

Variant links:

Genes affected

OR2T10 (HGNC:19573): (olfactory receptor family 2 subfamily T member 10) 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]

OR2T10 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=0.047107786).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T10	NM_001004693.2 linkuse as main transcript	c.929C>T	p.Pro310Leu	missense_variant	2/2	ENST00000642090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T10	ENST00000642090.1 linkuse as main transcript	c.929C>T	p.Pro310Leu	missense_variant	2/2		NM_001004693.2	P1
OR2T10	ENST00000330500.4 linkuse as main transcript	c.929C>T	p.Pro310Leu	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.00000699

AC:

AN:

143134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

230328

Hom.:

AF XY:

0.00000803

AC XY:

AN XY:

124530

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000311

AC:

AN:

1383212

Hom.:

Cov.:

AF XY:

0.0000319

AC XY:

AN XY:

688878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000407

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000699

AC:

AN:

143134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69780

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000336

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000253

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

Jan 03, 2022

The c.929C>T (p.P310L) alteration is located in exon 1 (coding exon 1) of the OR2T10 gene. This alteration results from a C to T substitution at nucleotide position 929, causing the proline (P) at amino acid position 310 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

0.075

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.8

DANN

Benign

0.79

DEOGEN2

Benign

0.0017

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.29

.;T

M_CAP

Benign

0.00069

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.96

.;N

REVEL

Benign

0.022

Sift

Benign

0.031

.;D

Sift4G

Uncertain

0.029

.;D

Polyphen

0.019

B;B

Vest4

0.11

MVP

0.12

MPC

0.059

ClinPred

0.046

GERP RS

-4.7

Varity_R

0.033

gMVP

0.067

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