rs679620

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -16 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_StrongBP6_Strong

The NM_002422.5(MMP3):c.133A>G (p.Lys45Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.526 (AC=846,122) in the gnomAD database across 1,608,044 control chromosomes, including 227,326 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.688. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★). This exact variant is curated in the UniProt human variants database as Uncertain Significance.

Frequency

Genomes: 𝑓 0.58 ( 25701 hom., cov: 31)

Exomes 𝑓: 0.52 ( 201625 hom. )

Consequence

MMP3
NM_002422.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.176

Publications

196 publications found

Variant links:

Genes affected

MMP3 (HGNC:7173): (matrix metallopeptidase 3) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. [provided by RefSeq, Jul 2008]

MMP3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002422.5, 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.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -16 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BP6

ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6884 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002422.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP3	NM_002422.5	MANE Select	c.133A>G	p.Lys45Glu	missense	Exon 2 of 10	NP_002413.1	P08254

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP3	ENST00000299855.10	TSL:1 MANE Select	c.133A>G	p.Lys45Glu	missense	Exon 2 of 10	ENSP00000299855.5	P08254
	MMP3	ENST00000524478.1	TSL:4	n.104A>G		non_coding_transcript_exon	Exon 2 of 4	ENSP00000435255.1	E9PKX2

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87307

AN:

151766

Hom.:

25663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.653

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.559

GnomAD2 exomes

AF:

0.580

AC:

142818

AN:

246160

AF XY:

0.576

show subpopulations

Gnomad AFR exome

AF:

0.653

Gnomad AMR exome

AF:

0.703

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.666

Gnomad FIN exome

AF:

0.589

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.551

GnomAD4 exome

AF:

0.521

AC:

758719

AN:

1456160

Hom.:

201625

Cov.:

AF XY:

0.526

AC XY:

380836

AN XY:

724274

show subpopulations

African (AFR)

AF:

0.659

AC:

21951

AN:

33328

American (AMR)

AF:

0.695

AC:

30762

AN:

44270

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

15862

AN:

26038

East Asian (EAS)

AF:

0.679

AC:

26897

AN:

39620

South Asian (SAS)

AF:

0.674

AC:

57923

AN:

85936

European-Finnish (FIN)

AF:

0.584

AC:

31084

AN:

53198

Middle Eastern (MID)

AF:

0.615

AC:

3534

AN:

5750

European-Non Finnish (NFE)

AF:

0.486

AC:

537959

AN:

1107874

Other (OTH)

AF:

0.544

AC:

32747

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

16292

32584

48877

65169

81461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16076

32152

48228

64304

80380

<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:

0.575

AC:

87403

AN:

151884

Hom.:

25701

Cov.:

AF XY:

0.584

AC XY:

43358

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.654

AC:

27068

AN:

41408

American (AMR)

AF:

0.639

AC:

9736

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

2131

AN:

3468

East Asian (EAS)

AF:

0.673

AC:

3471

AN:

5158

South Asian (SAS)

AF:

0.697

AC:

3353

AN:

4810

European-Finnish (FIN)

AF:

0.605

AC:

6367

AN:

10526

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.492

AC:

33402

AN:

67958

Other (OTH)

AF:

0.560

AC:

1182

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1834

3668

5503

7337

9171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.520

Hom.:

62752

Bravo

AF:

0.581

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.681

AC:

83619

AN:

122774

Turkish Variome

AF:

0.576

AC:

3866

AN:

6706

Hom.:

1134

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.659

AC:

5906

AN:

8960

Hom.:

1948

ABraOM SABE-WGS-1171

AF:

0.569

AC:

1332

AN:

2342

Hom.:

379

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.22

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.11

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.0030

MetaRNN

Benign

0.0000019

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.090

PhyloP100

-0.18

PrimateAI

Benign

0.30

PROVEAN

Benign

0.020

REVEL

Benign

0.0070

Sift

Benign

1.0

Sift4G

Benign

1.0

Varity_R

0.12

gMVP

0.49

Mutation Taster

=100/0

polymorphism (auto)

(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

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over