chr1-159440125-T-C

Position:

chr1-159440125-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012351.3(OR10J1):c.334T>C(p.Cys112Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

OR10J1
NM_012351.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.531

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10J1	NM_012351.3 linkuse as main transcript	c.334T>C	p.Cys112Arg	missense_variant	1/1	ENST00000423932.6	NP_036483.3	P30954A0A126GWQ9
OR10J1	NM_001363557.2 linkuse as main transcript	c.334T>C	p.Cys112Arg	missense_variant	5/5		NP_001350486.1
OR10J1	NM_001363558.2 linkuse as main transcript	c.334T>C	p.Cys112Arg	missense_variant	4/4		NP_001350487.1
OR10J1	XM_047417793.1 linkuse as main transcript	c.334T>C	p.Cys112Arg	missense_variant	2/2		XP_047273749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR10J1	ENST00000423932.6 linkuse as main transcript	c.334T>C	p.Cys112Arg	missense_variant	1/1	6	NM_012351.3	ENSP00000399078.4	A0A126GWQ9
ENSG00000228560	ENST00000431862.1 linkuse as main transcript	n.227+28717A>G		intron_variant		1
OR10J1	ENST00000641630.1 linkuse as main transcript	c.367T>C	p.Cys123Arg	missense_variant	1/1			ENSP00000492902.1	P30954
OR10J1	ENST00000642080.1 linkuse as main transcript	c.334T>C	p.Cys112Arg	missense_variant	2/2			ENSP00000493228.1	A0A126GWQ9

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152184

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251396

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135868

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:

0.0000462

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727230

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:

0.0000187

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

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 17, 2023

The c.367T>C (p.C123R) 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 367, causing the cysteine (C) at amino acid position 123 to be replaced by an arginine (R). 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

Pathogenic

0.75

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

.;T;.

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.47

.;T;T

M_CAP

Benign

0.0052

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

.;M;.

PrimateAI

Benign

0.22

REVEL

Benign

0.16

Polyphen

1.0

.;D;.

MutPred

0.75

.;Gain of glycosylation at T121 (P = 0.1939);.;

MVP

0.39

MPC

0.011

ClinPred

1.0

GERP RS

3.4

Varity_R

0.95

gMVP

0.39

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