rs193921073

chr19-8731906-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001004699.3(OR2Z1):c.878G>T(p.Arg293Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2Z1 NM_001004699.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.41

Genes affected

OR2Z1 (HGNC:15391): (olfactory receptor family 2 subfamily Z 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.932

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2Z1	NM_001004699.3	c.878G>T	p.Arg293Met	missense_variant	3/3	ENST00000641125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2Z1	ENST00000641125.1	c.878G>T	p.Arg293Met	missense_variant	3/3		NM_001004699.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	23
Dann	Benign	0.96
DEOGEN2	Benign	0.15	T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.036	N
M_CAP	Benign	0.0062	T
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	4.4	H;H
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.28	T
Polyphen		1.0	D;D
Vest4		0.55
MutPred		0.82		Loss of MoRF binding (P = 0.0586);Loss of MoRF binding (P = 0.0586);
MVP		0.82
MPC		0.24
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.86
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs193921073; hg19: chr19-8842268; COSMIC: COSV60691634; COSMIC: COSV60691634;