1-159439879-G-A

Position:

chr1-159439879-G-A

Variant summary

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

The NM_012351.3(OR10J1):c.88G>A(p.Val30Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,614,084 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

OR10J1
NM_012351.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.50

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=0.008535385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10J1	NM_012351.3 linkuse as main transcript	c.88G>A	p.Val30Met	missense_variant	1/1	ENST00000423932.6	NP_036483.3	P30954A0A126GWQ9
OR10J1	NM_001363557.2 linkuse as main transcript	c.88G>A	p.Val30Met	missense_variant	5/5		NP_001350486.1
OR10J1	NM_001363558.2 linkuse as main transcript	c.88G>A	p.Val30Met	missense_variant	4/4		NP_001350487.1
OR10J1	XM_047417793.1 linkuse as main transcript	c.88G>A	p.Val30Met	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.88G>A	p.Val30Met	missense_variant	1/1	6	NM_012351.3	ENSP00000399078.4	A0A126GWQ9
ENSG00000228560	ENST00000431862.1 linkuse as main transcript	n.227+28963C>T		intron_variant		1
OR10J1	ENST00000641630.1 linkuse as main transcript	c.121G>A	p.Val41Met	missense_variant	1/1			ENSP00000492902.1	P30954
OR10J1	ENST00000642080.1 linkuse as main transcript	c.88G>A	p.Val30Met	missense_variant	2/2			ENSP00000493228.1	A0A126GWQ9

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000386

AC:

AN:

251350

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00625

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000243

AC:

355

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

202

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00639

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.000355

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000599

Hom.:

Bravo

AF:

0.000480

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000346

AC:

EpiCase

AF:

0.000218

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.121G>A (p.V41M) alteration is located in exon 1 (coding exon 1) of the OR10J1 gene. This alteration results from a G to A substitution at nucleotide position 121, causing the valine (V) at amino acid position 41 to be replaced by a methionine (M). 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

-0.57

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.0

DANN

Benign

0.97

DEOGEN2

Benign

0.012

.;T;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.74

.;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0085

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.0

.;M;.

PrimateAI

Benign

0.20

REVEL

Benign

0.067

Polyphen

0.77

.;P;.

MVP

0.11

MPC

0.010

ClinPred

0.031

GERP RS

0.23

Varity_R

0.11

gMVP

0.056

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