chr1-159439967-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10J1	NM_012351.3	c.176T>G	p.Met59Arg	missense_variant	Exon 1 of 1	ENST00000423932.6	NP_036483.3
OR10J1	NM_001363557.2	c.176T>G	p.Met59Arg	missense_variant	Exon 5 of 5		NP_001350486.1
OR10J1	NM_001363558.2	c.176T>G	p.Met59Arg	missense_variant	Exon 4 of 4		NP_001350487.1
OR10J1	XM_047417793.1	c.176T>G	p.Met59Arg	missense_variant	Exon 2 of 2		XP_047273749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10J1	ENST00000423932.6	c.176T>G	p.Met59Arg	missense_variant	Exon 1 of 1	6	NM_012351.3	ENSP00000399078.4
ENSG00000228560	ENST00000431862.1	n.227+28875A>C		intron_variant	Intron 1 of 3	1
OR10J1	ENST00000641630.1	c.209T>G	p.Met70Arg	missense_variant	Exon 1 of 1			ENSP00000492902.1
OR10J1	ENST00000642080.1	c.176T>G	p.Met59Arg	missense_variant	Exon 2 of 2			ENSP00000493228.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251148 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135718

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 SAS exome AF: 0.0000327

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Pathogenic	3.5	.;M;.
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
Varity_R		0.98
gMVP		0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs35634161; hg19: chr1-159409757;