11-7796377-C-A

Variant names:

• chr11-7796377-C-A
• rs776149589
• NM_153444.1:c.566G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153444.1(OR5P2):​c.566G>T​(p.Ser189Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,604,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: OR5P2 NM_153444.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.59
• Publications: 1 publications found

Genes affected

OR5P2 (HGNC:14783): (olfactory receptor family 5 subfamily P 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]

ENSG00000271758 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153444.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5P2	NM_153444.1	MANE Select	c.566G>T	p.Ser189Ile	missense	Exon 1 of 1	NP_703145.1	A0A126GVJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5P2	ENST00000329434.3	TSL:6 MANE Select	c.566G>T	p.Ser189Ile	missense	Exon 1 of 1	ENSP00000331823.2	Q8WZ92
	ENSG00000271758	ENST00000527565.1	TSL:3	n.542+82630G>T		intron	N/A
	ENSG00000254951	ENST00000529488.5	TSL:5	n.532-41856G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000677 AC: 1 AN: 147648 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249406 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1457104 Hom.: 0 Cov.: 35 AF XY: 0.00000414 AC XY: 3 AN XY: 724976

African (AFR) AF: 0.00 AC: 0 AN: 31506

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39284

South Asian (SAS) AF: 0.00 AC: 0 AN: 85674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110614

Other (OTH) AF: 0.00 AC: 0 AN: 60158

GnomAD4 genome AF: 0.00000677 AC: 1 AN: 147648 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72042

African (AFR) AF: 0.0000266 AC: 1 AN: 37654

American (AMR) AF: 0.00 AC: 0 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5070

South Asian (SAS) AF: 0.00 AC: 0 AN: 4682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67836

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000166 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Benign	0.51
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.098	N
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-2.6
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.039
Sift	Benign	0.36	T
Sift4G	Benign	0.38	T
Polyphen		0.22	B
Vest4		0.10
MutPred		0.36		Loss of catalytic residue at S189 (P = 0.0222)
MVP		0.43
MPC		0.016
ClinPred		0.19	T
GERP RS		3.5
Varity_R		0.21
gMVP		0.18
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.40		Position offset: -12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs776149589; hg19: chr11-7817924;