11-58190711-C-G

Variant names:

• chr11-58190711-C-G
• rs1462827202
• NM_001005283.3:c.221C>G

Variant summary

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

The NM_001005283.3(OR9Q2):​c.221C>G​(p.Ser74Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. S74L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR9Q2 NM_001005283.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

Genes affected

OR9Q2 (HGNC:15328): (olfactory receptor family 9 subfamily Q 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

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 rank	MANE	Protein	UniProt
OR9Q2	NM_001005283.3	c.221C>G	p.Ser74Trp	missense_variant	Exon 2 of 2	ENST00000641291.1	NP_001005283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR9Q2	ENST00000641291.1	c.221C>G	p.Ser74Trp	missense_variant	Exon 2 of 2		NM_001005283.3	ENSP00000492924.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.97	.;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.9	H;H
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.9	.;D
REVEL	Benign	0.16
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		1.0	D;D
Vest4		0.51
MutPred		0.47		Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);
MVP		0.34
MPC		0.72
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.93
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1462827202; hg19: chr11-57958183;