11-56700922-G-C

Position:

• chr11-56700922-G-C

Variant summary

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

The NM_001005213.2(OR9G1):​c.535G>C​(p.Asp179His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 67)
• Consequence: OR9G1 NM_001005213.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.95

Genes affected

OR9G1 (HGNC:15319): (olfactory receptor family 9 subfamily G 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]

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	UniProt
OR9G1	NM_001005213.2	c.535G>C	p.Asp179His	missense_variant	2/2	ENST00000642097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR9G1	ENST00000642097.1	c.535G>C	p.Asp179His	missense_variant	2/2		NM_001005213.2	P1

Frequencies

GnomAD3 genomes Cov.: 67

GnomAD4 exome Cov.: 219

GnomAD4 genome Cov.: 67

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.535G>C (p.D179H) alteration is located in exon 1 (coding exon 1) of the OR9G1 gene. This alteration results from a G to C substitution at nucleotide position 535, causing the aspartic acid (D) at amino acid position 179 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.0073	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T;T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.0057	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	3.5	M;M
MutationTaster	Benign	0.98	D
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-6.6	.;D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		1.0	D;D
Vest4		0.65
MutPred		0.45		Gain of catalytic residue at L181 (P = 0.0511);Gain of catalytic residue at L181 (P = 0.0511);
MVP		0.53
MPC		0.0057
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.88
gMVP		0.25

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-56468398;