Variant 1-248592850-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004693.2(OR2T10):c.919G>A(p.Val307Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,546,246 control chromosomes in the GnomAD database, including 18 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 5 hom., cov: 29)

Exomes 𝑓: 0.00013 ( 13 hom. )

Consequence

OR2T10
NM_001004693.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.79

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031262994).

BP6

Variant 1-248592850-C-T is Benign according to our data. Variant chr1-248592850-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3302751.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T10	NM_001004693.2 linkuse as main transcript	c.919G>A	p.Val307Met	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.919G>A	p.Val307Met	missense_variant	2/2		NM_001004693.2	P1
OR2T10	ENST00000330500.4 linkuse as main transcript	c.919G>A	p.Val307Met	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

143094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00141

Gnomad SAS

AF:

0.000222

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000181

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000128

AC:

AN:

234272

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

126800

show subpopulations

Gnomad AFR exome

AF:

0.000138

Gnomad AMR exome

AF:

0.000126

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000229

Gnomad SAS exome

AF:

0.0000707

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.000131

AC:

184

AN:

1403028

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

698436

show subpopulations

Gnomad4 AFR exome

AF:

0.0000344

Gnomad4 AMR exome

AF:

0.0000968

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000623

Gnomad4 SAS exome

AF:

0.0000365

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.000209

AC:

AN:

143218

Hom.:

Cov.:

AF XY:

0.000200

AC XY:

AN XY:

69870

show subpopulations

Gnomad4 AFR

AF:

0.000220

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00141

Gnomad4 SAS

AF:

0.000222

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000181

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.000491

AC:

ESP6500EA

AF:

0.000354

AC:

ExAC

AF:

0.000135

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.17

DANN

Benign

0.37

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.28

.;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.055

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

0.090

.;N

REVEL

Benign

0.0050

Sift

Benign

0.14

.;T

Sift4G

Benign

0.14

.;T

Polyphen

0.027

B;B

Vest4

0.081

MVP

0.15

MPC

0.060

ClinPred

0.0046

GERP RS

-1.1

Varity_R

0.023

gMVP

0.028

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