rs972925

Positions:

• chr9-122614808-A-C
• chr9-122614808-A-G
• chr9-122614808-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012364.1(OR1Q1):​c.71A>C​(p.Gln24Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Q24R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: OR1Q1 NM_012364.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR1Q1	NM_012364.1	c.71A>C	p.Gln24Pro	missense_variant	1/1	ENST00000297913.3	NP_036496.1
LOC124902265	XR_007061759.1	n.344+4758A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR1Q1	ENST00000297913.3	c.71A>C	p.Gln24Pro	missense_variant	1/1	6	NM_012364.1	ENSP00000297913.2
ENSG00000234156	ENST00000431442.2	n.4767+4758A>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0042	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.17	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.62	P
Vest4		0.59
MutPred		0.47		Gain of glycosylation at Q24 (P = 0.0482);
MVP		0.55
MPC		0.20
ClinPred		0.87	D
GERP RS		2.9
Varity_R		0.77
gMVP		0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs972925; hg19: chr9-125377087;