NM_001004748.1:c.210G>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004748.1(OR51A2):c.210G>T(p.Met70Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000091 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000082 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR51A2
NM_001004748.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.22

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028194845).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR51A2	NM_001004748.1	MANE Select	c.210G>T	p.Met70Ile	missense	Exon 1 of 1	NP_001004748.1	Q8NGJ7
MMP26	NM_021801.5	MANE Select	c.-144-32564C>A		intron	N/A	NP_068573.2	Q9NRE1
MMP26	NM_001384608.1		c.-152-32766C>A		intron	N/A	NP_001371537.1	A0A8J8YUH5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR51A2	ENST00000380371.1	TSL:6 MANE Select	c.210G>T	p.Met70Ile	missense	Exon 1 of 1	ENSP00000369729.1	Q8NGJ7
MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-144-32564C>A		intron	N/A	ENSP00000369753.1	Q9NRE1
MMP26	ENST00000300762.2	TSL:1	c.-152-32766C>A		intron	N/A	ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes

AF:

0.0000911

AC:

AN:

120756

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000288

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000178

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:

0.000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000905

AC:

AN:

209870

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000382

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000653

Gnomad OTH exome

AF:

0.000388

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000825

AC:

AN:

1188394

Hom.:

Cov.:

AF XY:

0.0000704

AC XY:

AN XY:

596750

show subpopulations

African (AFR)

AF:

0.0000674

AC:

AN:

29666

American (AMR)

AF:

0.000370

AC:

AN:

37790

Ashkenazi Jewish (ASJ)

AF:

0.0000441

AC:

AN:

22692

East Asian (EAS)

AF:

0.00

AC:

AN:

36848

South Asian (SAS)

AF:

0.00

AC:

AN:

80790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4654

European-Non Finnish (NFE)

AF:

0.0000891

AC:

AN:

875126

Other (OTH)

AF:

0.0000583

AC:

AN:

51494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000910

AC:

AN:

120874

Hom.:

Cov.:

AF XY:

0.0000854

AC XY:

AN XY:

58552

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000287

AC:

AN:

34850

American (AMR)

AF:

0.000178

AC:

AN:

11262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2750

East Asian (EAS)

AF:

0.00

AC:

AN:

3838

South Asian (SAS)

AF:

0.00

AC:

AN:

3996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

256

European-Non Finnish (NFE)

AF:

0.000148

AC:

AN:

53884

Other (OTH)

AF:

0.00

AC:

AN:

1594

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000118818), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.302

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000241

Hom.:

ExAC

AF:

0.000111

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0020

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.00036

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.58

M_CAP

Benign

0.0050

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.5

PhyloP100

-5.2

PROVEAN

Benign

0.41

REVEL

Benign

0.010

Sift

Benign

0.27

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.026

MutPred

0.24

Loss of disorder (P = 0.0786)

MVP

0.27

MPC

1.2

ClinPred

0.034

GERP RS

-5.4

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.059

gMVP

0.13

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over