9-122553380-C-T

Variant names:

• chr9-122553380-C-T
• rs773511857
• NM_001004457.2:c.169C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004457.2(OR1N2):​c.169C>T​(p.His57Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: OR1N2 NM_001004457.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.616
• Publications: 1 publications found

Genes affected

OR1N2 (HGNC:15111): (olfactory receptor family 1 subfamily N member 2) 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]

OR1L8 (HGNC:15110): (olfactory receptor family 1 subfamily L member 8) 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]

ENSG00000234156 (HGNC:):

OR1J2 (HGNC:8209): (olfactory receptor family 1 subfamily J member 2) 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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15766174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004457.2. 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
	OR1N2	NM_001004457.2	MANE Select	c.169C>T	p.His57Tyr	missense	Exon 1 of 1	NP_001004457.2	Q8NGR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1N2	ENST00000373688.3	TSL:6 MANE Select	c.169C>T	p.His57Tyr	missense	Exon 1 of 1	ENSP00000362792.3	Q8NGR9
	ENSG00000234156	ENST00000431442.3	TSL:3	n.1362+50510C>T		intron	N/A
	ENSG00000234156	ENST00000723589.1		n.1045-53266C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251130 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461862 Hom.: 0 Cov.: 40 AF XY: 0.0000220 AC XY: 16 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000895 AC: 4 AN: 44716

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.0000113

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	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.62
PrimateAI	Benign	0.22	T
REVEL	Benign	0.091
Polyphen		0.47	P
MVP		0.35
MPC		0.21
ClinPred		0.36	T
GERP RS		2.5
PromoterAI		-0.0024	Neutral
Varity_R		0.13
gMVP		0.16
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs773511857; hg19: chr9-125315659;