Variant chr1-158399270-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004475.1(OR10T2):c.197T>C(p.Ile66Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,614,132 control chromosomes in the GnomAD database, including 1 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 0.00038 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

OR10T2
NM_001004475.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

OR10T2 (HGNC:14816): (olfactory receptor family 10 subfamily T member 2) 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]

OR10T2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03036359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10T2	NM_001004475.1 link	c.197T>C	p.Ile66Thr	missense_variant	1/1	ENST00000334438.1	NP_001004475.1	Q8NGX3A0A126GV74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10T2	ENST00000334438.1 link	c.197T>C	p.Ile66Thr	missense_variant	1/1	6	NM_001004475.1	ENSP00000334115.1		Q8NGX3

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000124

AC:

AN:

250878

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.0000289

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:

0.0000265

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000554

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.0000894

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:

0.00000630

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000381

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000621

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000173

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 30, 2024

The c.197T>C (p.I66T) alteration is located in exon 1 (coding exon 1) of the OR10T2 gene. This alteration results from a T to C substitution at nucleotide position 197, causing the isoleucine (I) at amino acid position 66 to be replaced by a threonine (T). 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

0.23

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0045

Eigen

Benign

0.14

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.57

M_CAP

Benign

0.0090

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.36

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.9

REVEL

Benign

0.095

Sift

Benign

0.12

Sift4G

Benign

0.40

Polyphen

0.95

Vest4

0.28

MVP

0.85

MPC

0.011

ClinPred

0.047

GERP RS

4.7

Varity_R

0.081

gMVP

0.038

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