chr9-122615605-T-C

Variant names:

• chr9-122615605-T-C
• rs775586362
• NM_012364.1:c.868T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012364.1(OR1Q1):​c.868T>C​(p.Tyr290His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000969 in 1,444,074 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y290N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: OR1Q1 NM_012364.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.87
• Publications: 0 publications found

Genes affected

OR1Q1 (HGNC:8223): (olfactory receptor family 1 subfamily Q 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]

ENSG00000234156 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.922

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012364.1. 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
	OR1Q1	NM_012364.1	MANE Select	c.868T>C	p.Tyr290His	missense	Exon 1 of 1	NP_036496.1	Q15612

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1Q1	ENST00000297913.3	TSL:6 MANE Select	c.868T>C	p.Tyr290His	missense	Exon 1 of 1	ENSP00000297913.2	Q15612
	ENSG00000234156	ENST00000431442.3	TSL:3	n.4767+5555T>C		intron	N/A
	ENSG00000234156	ENST00000723590.1		n.801+8656T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000969 AC: 14 AN: 1444074 Hom.: 0 Cov.: 35 AF XY: 0.00000836 AC XY: 6 AN XY: 717540

African (AFR) AF: 0.00 AC: 0 AN: 32790

American (AMR) AF: 0.0000241 AC: 1 AN: 41532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24618

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 82506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1105264

Other (OTH) AF: 0.00 AC: 0 AN: 59564

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	-0.030	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		7.9
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-4.1	D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.74		Gain of disorder (P = 0.0515)
MVP		0.84
MPC		0.70
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.91
gMVP		0.46
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs775586362; hg19: chr9-125377884;