NM_001004748.1:c.740G>A

Variant names:

• chr11-4954974-C-T
• rs752232056
• NM_001004748.1:c.740G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004748.1(OR51A2):​c.740G>A​(p.Cys247Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 18)
• Consequence: OR51A2 NM_001004748.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0960
• Publications: 0 publications found

Genes affected

OR51A2 (HGNC:14764): (olfactory receptor family 51 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]

MMP26 (HGNC:14249): (matrix metallopeptidase 26) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3066733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004748.1. 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
	OR51A2	NM_001004748.1	MANE Select	c.740G>A	p.Cys247Tyr	missense	Exon 1 of 1	NP_001004748.1	Q8NGJ7
	MMP26	NM_021801.5	MANE Select	c.-144-33094C>T		intron	N/A	NP_068573.2	Q9NRE1
	MMP26	NM_001384608.1		c.-152-33296C>T		intron	N/A	NP_001371537.1	A0A8J8YUH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR51A2	ENST00000380371.1	TSL:6 MANE Select	c.740G>A	p.Cys247Tyr	missense	Exon 1 of 1	ENSP00000369729.1	Q8NGJ7
	MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-144-33094C>T		intron	N/A	ENSP00000369753.1	Q9NRE1
	MMP26	ENST00000300762.2	TSL:1	c.-152-33296C>T		intron	N/A	ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 18

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	0.16
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	-0.033
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		0.096
PROVEAN	Pathogenic	-8.3	D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.23
MutPred		0.41		Gain of catalytic residue at I246 (P = 0.0882)
MVP		0.59
MPC		2.8
ClinPred		1.0	D
GERP RS		3.3
Varity_R		0.92
gMVP		0.15
Mutation Taster		=94/6	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: rs752232056; hg19: chr11-4976204;