1-159439898-T-C

Variant names:

Variant summary

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

The NM_012351.3(OR10J1):c.107T>C(p.Ile36Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

OR10J1
NM_012351.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Variant links:

Genes affected

OR10J1 (HGNC:8175): (olfactory receptor family 10 subfamily J member 1) 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]

OR10J1 links:

ENSG00000228560 (HGNC:):

ENSG00000228560 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=0.03588763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10J1	NM_012351.3 link	c.107T>C	p.Ile36Thr	missense_variant	Exon 1 of 1	ENST00000423932.6	NP_036483.3	P30954A0A126GWQ9
OR10J1	NM_001363557.2 link	c.107T>C	p.Ile36Thr	missense_variant	Exon 5 of 5		NP_001350486.1
OR10J1	NM_001363558.2 link	c.107T>C	p.Ile36Thr	missense_variant	Exon 4 of 4		NP_001350487.1
OR10J1	XM_047417793.1 link	c.107T>C	p.Ile36Thr	missense_variant	Exon 2 of 2		XP_047273749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR10J1	ENST00000423932.6 link	c.107T>C	p.Ile36Thr	missense_variant	Exon 1 of 1	6	NM_012351.3	ENSP00000399078.4	A0A126GWQ9
ENSG00000228560	ENST00000431862.1 link	n.227+28944A>G		intron_variant	Intron 1 of 3	1
OR10J1	ENST00000641630.1 link	c.140T>C	p.Ile47Thr	missense_variant	Exon 1 of 1			ENSP00000492902.1	P30954
OR10J1	ENST00000642080.1 link	c.107T>C	p.Ile36Thr	missense_variant	Exon 2 of 2			ENSP00000493228.1	A0A126GWQ9

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00115

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:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251378

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.140T>C (p.I47T) alteration is located in exon 1 (coding exon 1) of the OR10J1 gene. This alteration results from a T to C substitution at nucleotide position 140, causing the isoleucine (I) at amino acid position 47 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

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.1

DANN

Benign

0.83

DEOGEN2

Benign

0.012

.;T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.74

.;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.036

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.24

.;N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.5

.;.;N

REVEL

Benign

0.061

Sift

Benign

0.33

.;.;T

Polyphen

0.0040

.;B;.

MutPred

0.44

.;Loss of stability (P = 0.0084);.;

MVP

0.17

MPC

0.0059

ClinPred

0.31

GERP RS

3.2

Varity_R

0.068

gMVP

0.051

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