dbSNP rs3743563: MMP15:p.Gly609Arg (chr16-58045261-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002428.4(MMP15):c.1825G>A(p.Gly609Arg) variant causes a missense change. The variant allele was found at a frequency of 0.217 in 1,608,266 control chromosomes in the GnomAD database, including 41,416 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3364 hom., cov: 33)

Exomes 𝑓: 0.22 ( 38052 hom. )

Consequence

MMP15
NM_002428.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.84

Publications

34 publications found

Variant links:

Genes affected

MMP15 (HGNC:7161): (matrix metallopeptidase 15) This gene encodes a member of the peptidase M10 family and membrane-type subfamily of matrix metalloproteinases (MMPs). Proteins in this 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. Members of this subfamily contain a transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. The encoded preproprotein is proteolytically processed to generate the mature protease. This protein may play a role in cancer progression. [provided by RefSeq, Jan 2016]

MMP15 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002428.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037374198).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002428.4. 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
	MMP15	NM_002428.4	MANE Select	c.1825G>A	p.Gly609Arg	missense	Exon 10 of 10	NP_002419.1	P51511

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP15	ENST00000219271.4	TSL:1 MANE Select	c.1825G>A	p.Gly609Arg	missense	Exon 10 of 10	ENSP00000219271.3	P51511
MMP15	ENST00000930621.1		c.2176G>A	p.Gly726Arg	missense	Exon 11 of 11	ENSP00000600680.1
MMP15	ENST00000907594.1		c.1885G>A	p.Gly629Arg	missense	Exon 10 of 10	ENSP00000577653.1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28400

AN:

152108

Hom.:

3355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0649

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.170

GnomAD2 exomes

AF:

0.237

AC:

56369

AN:

237644

AF XY:

0.227

show subpopulations

Gnomad AFR exome

AF:

0.0614

Gnomad AMR exome

AF:

0.441

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.341

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.220

AC:

319777

AN:

1456040

Hom.:

38052

Cov.:

AF XY:

0.216

AC XY:

156602

AN XY:

723798

show subpopulations

African (AFR)

AF:

0.0537

AC:

1795

AN:

33418

American (AMR)

AF:

0.425

AC:

18691

AN:

43944

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

3008

AN:

25864

East Asian (EAS)

AF:

0.348

AC:

13751

AN:

39468

South Asian (SAS)

AF:

0.170

AC:

14501

AN:

85140

European-Finnish (FIN)

AF:

0.310

AC:

16377

AN:

52776

Middle Eastern (MID)

AF:

0.0956

AC:

466

AN:

4876

European-Non Finnish (NFE)

AF:

0.215

AC:

239138

AN:

1110454

Other (OTH)

AF:

0.200

AC:

12050

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

15400

30799

46199

61598

76998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8432

16864

25296

33728

42160

<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

AF:

0.187

AC:

28421

AN:

152226

Hom.:

3364

Cov.:

AF XY:

0.194

AC XY:

14435

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0648

AC:

2692

AN:

41556

American (AMR)

AF:

0.304

AC:

4654

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

424

AN:

3472

East Asian (EAS)

AF:

0.342

AC:

1772

AN:

5184

South Asian (SAS)

AF:

0.174

AC:

840

AN:

4832

European-Finnish (FIN)

AF:

0.312

AC:

3306

AN:

10602

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14183

AN:

67968

Other (OTH)

AF:

0.169

AC:

357

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1173

2346

3519

4692

5865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<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:

0.193

Hom.:

1949

Bravo

AF:

0.185

Asia WGS

AF:

0.254

AC:

884

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

PhyloP100

5.8

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.1

REVEL

Benign

0.038

Sift

Benign

0.075

Sift4G

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.1

Varity_R

0.091

gMVP

0.37

Mutation Taster

=93/7

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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