1-159439967-T-G

Variant names:

• chr1-159439967-T-G
• rs35634161
• NM_012351.3:c.176T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012351.3(OR10J1):​c.176T>G​(p.Met59Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR10J1 NM_012351.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00
• Publications: 12 publications found

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]

ENSG00000228560 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012351.3. 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
	OR10J1	NM_012351.3	MANE Select	c.176T>G	p.Met59Arg	missense	Exon 1 of 1	NP_036483.3	A0A126GWQ9
	OR10J1	NM_001363557.2		c.176T>G	p.Met59Arg	missense	Exon 5 of 5	NP_001350486.1	A0A126GWQ9
	OR10J1	NM_001363558.2		c.176T>G	p.Met59Arg	missense	Exon 4 of 4	NP_001350487.1	A0A126GWQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10J1	ENST00000423932.6	TSL:6 MANE Select	c.176T>G	p.Met59Arg	missense	Exon 1 of 1	ENSP00000399078.4	A0A126GWQ9
	ENSG00000228560	ENST00000431862.1	TSL:1	n.227+28875A>C		intron	N/A
	OR10J1	ENST00000641630.1		c.209T>G	p.Met70Arg	missense	Exon 1 of 1	ENSP00000492902.1	P30954

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251148 AF XY: 0.00000737

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 64 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

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

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0046	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		5.0
PrimateAI	Benign	0.22	T
REVEL	Benign	0.28
Polyphen		0.76	P
MutPred		0.72		Gain of methylation at M70 (P = 0.0116)
MVP		0.46
MPC		0.011
ClinPred		0.99	D
GERP RS		4.5
PromoterAI		0.013	Neutral
Varity_R		0.98
gMVP		0.35
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.46		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35634161; hg19: chr1-159409757;