11-4955515-T-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004748.1(OR51A2):c.199A>C(p.Met67Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000335 in 1,194,914 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M67T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 17)

Exomes 𝑓: 0.0000033 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

OR51A2
NM_001004748.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Publications

0 publications found

Variant links:

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]

OR51A2 links:

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]

MMP26 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.19068825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51A2	NM_001004748.1 link	c.199A>C	p.Met67Leu	missense_variant	Exon 1 of 1	ENST00000380371.1	NP_001004748.1	Q8NGJ7A0A126GWD5
MMP26	NM_021801.5 link	c.-144-32553T>G		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2	Q9NRE1
MMP26	NM_001384608.1 link	c.-152-32755T>G		intron_variant	Intron 2 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR51A2	ENST00000380371.1 link	c.199A>C	p.Met67Leu	missense_variant	Exon 1 of 1	6	NM_001004748.1	ENSP00000369729.1	Q8NGJ7
MMP26	ENST00000380390.6 link	c.-144-32553T>G		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1	Q9NRE1
MMP26	ENST00000300762.2 link	c.-152-32755T>G		intron_variant	Intron 2 of 7	1		ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

123278

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000335

AC:

AN:

1194914

Hom.:

Cov.:

AF XY:

0.00000500

AC XY:

AN XY:

600198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29760

American (AMR)

AF:

0.00

AC:

AN:

37920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22738

East Asian (EAS)

AF:

0.00

AC:

AN:

37028

South Asian (SAS)

AF:

0.0000494

AC:

AN:

80894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4688

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

879906

Other (OTH)

AF:

0.00

AC:

AN:

51672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

123278

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

59506

African (AFR)

AF:

0.00

AC:

AN:

35128

American (AMR)

AF:

0.00

AC:

AN:

11510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2854

East Asian (EAS)

AF:

0.00

AC:

AN:

3940

South Asian (SAS)

AF:

0.00

AC:

AN:

4000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

55354

Other (OTH)

AF:

0.00

AC:

AN:

1622

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 13, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.199A>C (p.M67L) alteration is located in exon 1 (coding exon 1) of the OR51A2 gene. This alteration results from a A to C substitution at nucleotide position 199, causing the methionine (M) at amino acid position 67 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0099

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.73

M_CAP

Benign

0.0045

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.2

PhyloP100

1.3

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.031

Sift

Uncertain

0.014

Sift4G

Benign

0.073

Polyphen

0.0030

Vest4

0.20

MutPred

0.49

Loss of disorder (P = 0.2368);

MVP

0.41

MPC

1.1

ClinPred

0.067

GERP RS

1.7

PromoterAI

-0.0045

Neutral

(source)

Varity_R

0.27

gMVP

0.36

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over