11-4955219-T-G

Variant names:

• chr11-4955219-T-G
• rs766971113
• NM_001004748.1:c.495A>C

Variant summary

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

The NM_001004748.1(OR51A2):​c.495A>C​(p.Leu165Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000028 (1 hom., cov: 16)
  • Exomes 𝑓: 0.0000017 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR51A2 NM_001004748.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.61
• Publications: 1 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 0 ACMG points.

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.495A>C	p.Leu165Phe	missense	Exon 1 of 1	NP_001004748.1	Q8NGJ7
	MMP26	NM_021801.5	MANE Select	c.-144-32849T>G		intron	N/A	NP_068573.2	Q9NRE1
	MMP26	NM_001384608.1		c.-152-33051T>G		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.495A>C	p.Leu165Phe	missense	Exon 1 of 1	ENSP00000369729.1	Q8NGJ7
	MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-144-32849T>G		intron	N/A	ENSP00000369753.1	Q9NRE1
	MMP26	ENST00000300762.2	TSL:1	c.-152-33051T>G		intron	N/A	ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes AF: 0.0000277 AC: 3 AN: 108320 Hom.: 1 Cov.: 16

Gnomad AFR AF: 0.0000922

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: 0.00000487 AC: 1 AN: 205226 AF XY: 0.00000900

Gnomad AFR exome AF: 0.0000691

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000172 AC: 2 AN: 1162726 Hom.: 1 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 582888

African (AFR) AF: 0.00 AC: 0 AN: 29588

American (AMR) AF: 0.00 AC: 0 AN: 35220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22254

East Asian (EAS) AF: 0.00 AC: 0 AN: 32508

South Asian (SAS) AF: 0.00 AC: 0 AN: 79516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 863290

Other (OTH) AF: 0.0000401 AC: 2 AN: 49884

GnomAD4 genome AF: 0.0000277 AC: 3 AN: 108320 Hom.: 1 Cov.: 16 AF XY: 0.0000381 AC XY: 2 AN XY: 52434

African (AFR) AF: 0.0000922 AC: 3 AN: 32548

American (AMR) AF: 0.00 AC: 0 AN: 9746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2422

East Asian (EAS) AF: 0.00 AC: 0 AN: 3274

South Asian (SAS) AF: 0.00 AC: 0 AN: 3710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 47674

Other (OTH) AF: 0.00 AC: 0 AN: 1416

Alfa AF: 0.0000843 Hom.: 0

ExAC AF: 0.00000902 AC: 1

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	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0091	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		-2.6
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.56		Gain of methylation at R166 (P = 0.1073)
MVP		0.88
MPC		2.4
ClinPred		0.46	T
GERP RS		-0.84
PromoterAI		0.038	Neutral
Varity_R		0.36
gMVP		0.079
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: -3

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

Other links and lift over

dbSNP: rs766971113; hg19: chr11-4976449;