11-59422002-A-G

Variant names:

• chr11-59422002-A-G
• rs1858228427
• NM_001001954.2:c.952T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001954.2(OR5A2):​c.952T>C​(p.Phe318Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,752 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: OR5A2 NM_001001954.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.684
• Publications: 0 publications found

Genes affected

OR5A2 (HGNC:15249): (olfactory receptor family 5 subfamily A 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07278791).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001954.2. 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
	OR5A2	NM_001001954.2	MANE Select	c.952T>C	p.Phe318Leu	missense	Exon 2 of 2	NP_001001954.1	A0A126GVD5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5A2	ENST00000302040.6	TSL:6 MANE Select	c.952T>C	p.Phe318Leu	missense	Exon 2 of 2	ENSP00000303834.4	Q8NGI9
	OR5A2	ENST00000641361.1		c.952T>C	p.Phe318Leu	missense	Exon 2 of 2	ENSP00000493065.1	Q8NGI9
	OR5A2	ENST00000641673.1		c.952T>C	p.Phe318Leu	missense	Exon 1 of 1	ENSP00000492975.1	Q8NGI9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456752 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724180

African (AFR) AF: 0.00 AC: 0 AN: 33310

American (AMR) AF: 0.00 AC: 0 AN: 44272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 85656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1109014

Other (OTH) AF: 0.00 AC: 0 AN: 60172

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.38
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.68
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.049
Sift	Benign	0.18	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.080
MutPred		0.48		Gain of disorder (P = 0.1562)
MVP		0.067
MPC		0.032
ClinPred		0.065	T
GERP RS		2.2
Varity_R		0.062
gMVP		0.19
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1858228427; hg19: chr11-59189475;