11-58119227-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005211.2(OR9I1):c.218A>G(p.Tyr73Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR9I1 NM_001005211.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.691

Genes affected

OR9I1 (HGNC:14718): (olfactory receptor family 9 subfamily I 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]

OR9Q1 (HGNC:14724): (olfactory receptor family 9 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20896783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR9I1	NM_001005211.2	c.218A>G	p.Tyr73Cys	missense_variant	3/3	ENST00000641439.1
OR9Q1	NM_001005212.4	c.-14-60204T>C		intron_variant		ENST00000335397.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR9I1	ENST00000641439.1	c.218A>G	p.Tyr73Cys	missense_variant	3/3		NM_001005211.2	P1
OR9Q1	ENST00000335397.3	c.-14-60204T>C		intron_variant			NM_001005212.4	P1
OR9I1	ENST00000641478.1	c.218A>G	p.Tyr73Cys	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Richard Lifton Laboratory, Yale University School of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.026	T;T;T
Eigen	Benign	0.060
Eigen_PC	Benign	0.044
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.28	T
Polyphen		0.84	P;P;P
Vest4		0.36
MutPred		0.44		Loss of catalytic residue at L68 (P = 0.0848);Loss of catalytic residue at L68 (P = 0.0848);Loss of catalytic residue at L68 (P = 0.0848);
MVP		0.13
MPC		0.040
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.34
gMVP		0.30

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: rs386352342; hg19: chr11-57886699;