11-7796077-C-T

Variant names:

• chr11-7796077-C-T
• rs1857346630
• NM_153444.1:c.866G>A

Variant summary

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

The NM_153444.1(OR5P2):​c.866G>A​(p.Arg289Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000677 in 147,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000068 (0 hom., cov: 31)
• Consequence: OR5P2 NM_153444.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02

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

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, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5P2	NM_153444.1	c.866G>A	p.Arg289Lys	missense_variant	Exon 1 of 1	ENST00000329434.3	NP_703145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5P2	ENST00000329434.3	c.866G>A	p.Arg289Lys	missense_variant	Exon 1 of 1	6	NM_153444.1	ENSP00000331823.2
ENSG00000271758	ENST00000527565.1	n.542+82930G>A		intron_variant	Intron 5 of 5	3
ENSG00000254951	ENST00000529488.5	n.532-41556G>A		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.00000677 AC: 1 AN: 147662 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

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

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000677 AC: 1 AN: 147662 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1 AN XY: 72040

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000663

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.866G>A (p.R289K) alteration is located in exon 1 (coding exon 1) of the OR5P2 gene. This alteration results from a G to A substitution at nucleotide position 866, causing the arginine (R) at amino acid position 289 to be replaced by a lysine (K). 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	0.19
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.0056
Eigen_PC	Benign	0.084
FATHMM_MKL	Benign	0.24	N
M_CAP	Benign	0.0072	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.13
Sift	Benign	0.078	T
Sift4G	Uncertain	0.040	D
Polyphen		0.55	P
Vest4		0.73
MutPred		0.80		Gain of methylation at R289 (P = 0.0122);
MVP		0.66
MPC		0.0093
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.41
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1857346630; hg19: chr11-7817624;