NM_153444.1:c.754A>C

Variant names:

• chr11-7796189-T-G
• rs762072377
• NM_153444.1:c.754A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_153444.1(OR5P2):​c.754A>C​(p.Thr252Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,604,710 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (1 hom., cov: 31)
  • Exomes 𝑓: 0.000030 (4 hom.)
• Consequence: OR5P2 NM_153444.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.351
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31821704).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.754A>C	p.Thr252Pro	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.754A>C	p.Thr252Pro	missense	Exon 1 of 1	ENSP00000331823.2	Q8WZ92
	ENSG00000271758	ENST00000527565.1	TSL:3	n.542+82818A>C		intron	N/A
	ENSG00000254951	ENST00000529488.5	TSL:5	n.532-41668A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000272 AC: 4 AN: 147178 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000590

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000400 AC: 10 AN: 249690 AF XY: 0.0000370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000302 AC: 44 AN: 1457532 Hom.: 4 Cov.: 35 AF XY: 0.0000359 AC XY: 26 AN XY: 725144

African (AFR) AF: 0.00 AC: 0 AN: 31564

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39294

South Asian (SAS) AF: 0.00 AC: 0 AN: 85702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

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

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1110908

Other (OTH) AF: 0.0000332 AC: 2 AN: 60178

GnomAD4 genome AF: 0.0000272 AC: 4 AN: 147178 Hom.: 1 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 71808

African (AFR) AF: 0.00 AC: 0 AN: 37386

American (AMR) AF: 0.00 AC: 0 AN: 15044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5038

South Asian (SAS) AF: 0.00 AC: 0 AN: 4646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000590 AC: 4 AN: 67758

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000414 AC: 5

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.010
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.35
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.20
Sift	Benign	0.063	T
Sift4G	Benign	0.086	T
Polyphen		0.96	P
Vest4		0.39
MutPred		0.35		Gain of sheet (P = 0.0827)
MVP		0.56
MPC		0.020
ClinPred		0.58	D
GERP RS		4.3
Varity_R		0.95
gMVP		0.36
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs762072377; hg19: chr11-7817736;