rs139662085

Variant names:

• chr1-159535422-T-C
• rs139662085
• NM_001004469.1:c.586A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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. 15/24 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.614
• Publications: 5 publications found

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]

ENSG00000289484 (HGNC:):

LINC02819 (HGNC:54350): (long intergenic non-protein coding RNA 2819)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004469.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10J5	NM_001004469.1	MANE Select	c.586A>G	p.Ile196Val	missense	Exon 1 of 1	NP_001004469.1	A0A126GV70

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10J5	ENST00000334857.3	TSL:6 MANE Select	c.586A>G	p.Ile196Val	missense	Exon 1 of 1	ENSP00000334441.2	Q8NHC4
	ENSG00000289484	ENST00000693113.1		n.755-32147A>G		intron	N/A
	LINC02819	ENST00000732995.1		n.454+15121T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152182 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000343 AC: 86 AN: 250830 AF XY: 0.000354

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 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.: 1 Cov.: 33 AF XY: 0.000492 AC XY: 358 AN XY: 727188

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000185 AC: 16 AN: 86254

European-Finnish (FIN) AF: 0.000543 AC: 29 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000596 AC: 663 AN: 1111892

Other (OTH) AF: 0.000431 AC: 26 AN: 60388

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33 AN XY: 74470

African (AFR) AF: 0.0000722 AC: 3 AN: 41568

American (AMR) AF: 0.000327 AC: 5 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 68016

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000460 Hom.: 0

Bravo AF: 0.000276

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000379 AC: 46

EpiCase AF: 0.000491

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.61
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.042
Sift	Benign	0.051	T
Sift4G	Benign	0.23	T
Polyphen		0.053	B
Vest4		0.042
MVP		0.24
MPC		0.15
ClinPred		0.019	T
GERP RS		3.0
Varity_R		0.13
gMVP		0.034
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs139662085; hg19: chr1-159505212;