rs193921073

Variant names:

• chr19-8731906-G-A
• NM_001004699.3:c.878G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-8731906-G-A
• chr19-8731906-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001004699.3(OR2Z1):​c.878G>A​(p.Arg293Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OR2Z1 NM_001004699.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2Z1	NM_001004699.3	c.878G>A	p.Arg293Lys	missense_variant	Exon 3 of 3	ENST00000641125.1	NP_001004699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2Z1	ENST00000641125.1	c.878G>A	p.Arg293Lys	missense_variant	Exon 3 of 3		NM_001004699.3	ENSP00000493322.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.0051	T
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.5	.;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.015	.;D
Sift4G	Uncertain	0.013	.;D
Polyphen		1.0	D;D
Vest4		0.28
MutPred		0.82		Gain of methylation at R293 (P = 0.0115);Gain of methylation at R293 (P = 0.0115);
MVP		0.79
MPC		0.14
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.65
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr19-8842268;