Genetic Variant OR10J1:p.Met59Thr (chr1-159439967-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012351.3(OR10J1):c.176T>C(p.Met59Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0176 in 1,614,140 control chromosomes in the GnomAD database, including 394 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 52 hom., cov: 32)

Exomes 𝑓: 0.018 ( 342 hom. )

Consequence

OR10J1
NM_012351.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.00

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011399478).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10J1	NM_012351.3 link	c.176T>C	p.Met59Thr	missense_variant	Exon 1 of 1	ENST00000423932.6	NP_036483.3	P30954A0A126GWQ9
OR10J1	NM_001363557.2 link	c.176T>C	p.Met59Thr	missense_variant	Exon 5 of 5		NP_001350486.1
OR10J1	NM_001363558.2 link	c.176T>C	p.Met59Thr	missense_variant	Exon 4 of 4		NP_001350487.1
OR10J1	XM_047417793.1 link	c.176T>C	p.Met59Thr	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.176T>C	p.Met59Thr	missense_variant	Exon 1 of 1	6	NM_012351.3	ENSP00000399078.4	A0A126GWQ9
ENSG00000228560	ENST00000431862.1 link	n.227+28875A>G		intron_variant	Intron 1 of 3	1
OR10J1	ENST00000641630.1 link	c.209T>C	p.Met70Thr	missense_variant	Exon 1 of 1			ENSP00000492902.1	P30954
OR10J1	ENST00000642080.1 link	c.176T>C	p.Met59Thr	missense_variant	Exon 2 of 2			ENSP00000493228.1	A0A126GWQ9

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2352

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00969

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.0618

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.0440

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0195

AC:

4892

AN:

251148

AF XY:

0.0193

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00570

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.0578

Gnomad FIN exome

AF:

0.0418

Gnomad NFE exome

AF:

0.0197

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0178

AC:

26040

AN:

1461844

Hom.:

342

Cov.:

AF XY:

0.0176

AC XY:

12807

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

33478

American (AMR)

AF:

0.00595

AC:

266

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00214

AC:

AN:

26136

East Asian (EAS)

AF:

0.0765

AC:

3038

AN:

39700

South Asian (SAS)

AF:

0.0103

AC:

889

AN:

86256

European-Finnish (FIN)

AF:

0.0402

AC:

2148

AN:

53420

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0167

AC:

18566

AN:

1111984

Other (OTH)

AF:

0.0161

AC:

974

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1661

3322

4982

6643

8304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

700

1400

2100

2800

3500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0154

AC:

2351

AN:

152296

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1216

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00262

AC:

109

AN:

41570

American (AMR)

AF:

0.00967

AC:

148

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.0616

AC:

319

AN:

5180

South Asian (SAS)

AF:

0.00932

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0440

AC:

467

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0181

AC:

1233

AN:

68016

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

121

242

362

483

604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0174

Hom.:

110

Bravo

AF:

0.0126

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0182

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.0187

AC:

161

ExAC

AF:

0.0202

AC:

2452

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0133

EpiControl

AF:

0.0130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0064

.;T;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.4

.;M;.

PhyloP100

5.0

PrimateAI

Benign

0.23

REVEL

Benign

0.21

Polyphen

1.0

.;D;.

MPC

0.012

ClinPred

0.061

GERP RS

4.5

PromoterAI

0.040

Neutral

(source)

Varity_R

0.91

gMVP

0.090

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over