Variant 1-159535422-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001004469.1(OR10J5):c.586A>G(p.Ile196Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000502 in 1,614,048 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 1 hom. )

Consequence

OR10J5
NM_001004469.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.614

Variant links:

Genes affected

OR10J5 (HGNC:14993): (olfactory receptor family 10 subfamily J member 5) 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]

OR10J5 links:

(HGNC:):

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
OR10J5	NM_001004469.1 linkuse as main transcript	c.586A>G	p.Ile196Val	missense_variant	1/1	ENST00000334857.3	NP_001004469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10J5	ENST00000334857.3 linkuse as main transcript	c.586A>G	p.Ile196Val	missense_variant	1/1		NM_001004469.1	ENSP00000334441	P1
	ENST00000693113.1 linkuse as main transcript	n.755-32147A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000343

AC:

AN:

250830

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.000565

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000514

AC:

752

AN:

1461748

Hom.:

Cov.:

AF XY:

0.000492

AC XY:

358

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.000596

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000381

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000454

Hom.:

Bravo

AF:

0.000276

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000711

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

Apr 15, 2024

The c.586A>G (p.I196V) alteration is located in exon 1 (coding exon 1) of the OR10J5 gene. This alteration results from a A to G substitution at nucleotide position 586, causing the isoleucine (I) at amino acid position 196 to be replaced by a valine (V). 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

0.097

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.022

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.60

M_CAP

Benign

0.0023

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.99

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.80

REVEL

Benign

0.042

Sift

Benign

0.051

Sift4G

Benign

0.23

Polyphen

0.053

Vest4

0.042

MVP

0.24

MPC

0.15

ClinPred

0.019

GERP RS

3.0

Varity_R

0.13

gMVP

0.034

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.47

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.47

Position offset: 1

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