Variant 1-248593387-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001004693.2(OR2T10):c.382C>T(p.His128Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,572,642 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 28)

Exomes 𝑓: 0.00013 ( 26 hom. )

Consequence

OR2T10
NM_001004693.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.636

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.071881086).

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T10	NM_001004693.2 linkuse as main transcript	c.382C>T	p.His128Tyr	missense_variant	2/2	ENST00000642090.1	NP_001004693.1	Q8NGZ9A0A126GV79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T10	ENST00000642090.1 linkuse as main transcript	c.382C>T	p.His128Tyr	missense_variant	2/2		NM_001004693.2	ENSP00000493236.1		Q8NGZ9
OR2T10	ENST00000330500.4 linkuse as main transcript	c.382C>T	p.His128Tyr	missense_variant	1/1	6		ENSP00000329210.2		Q8NGZ9

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

142104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000280

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000205

Gnomad ASJ

AF:

0.000588

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000136

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000192

AC:

AN:

245022

Hom.:

AF XY:

0.000173

AC XY:

AN XY:

132654

show subpopulations

Gnomad AFR exome

AF:

0.000135

Gnomad AMR exome

AF:

0.0000592

Gnomad ASJ exome

AF:

0.000603

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.0000480

Gnomad NFE exome

AF:

0.000269

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000129

AC:

185

AN:

1430538

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

711878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000687

Gnomad4 ASJ exome

AF:

0.000388

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000107

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.000106

AC:

AN:

142104

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

69170

show subpopulations

Gnomad4 AFR

AF:

0.0000280

Gnomad4 AMR

AF:

0.000205

Gnomad4 ASJ

AF:

0.000588

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000136

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000267

Hom.:

ExAC

AF:

0.000101

AC:

EpiCase

AF:

0.000277

EpiControl

AF:

0.000181

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 09, 2021

The c.382C>T (p.H128Y) 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 382, causing the histidine (H) at amino acid position 128 to be replaced by a tyrosine (Y). 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

-0.50

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.19

.;T

M_CAP

Benign

0.00074

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.0

.;D

REVEL

Benign

0.041

Sift

Benign

0.17

.;T

Sift4G

Benign

0.11

.;T

Polyphen

0.0010

B;B

Vest4

0.19

MVP

0.23

MPC

0.070

ClinPred

0.0086

GERP RS

1.3

Varity_R

0.13

gMVP

0.095

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