Genetic Variant MMP3:c.626-14A>G (chr11-102840607-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002422.5(MMP3):c.626-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,611,110 control chromosomes in the GnomAD database, including 226,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25211 hom., cov: 32)

Exomes 𝑓: 0.52 ( 201738 hom. )

Consequence

MMP3
NM_002422.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.986

Publications

51 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-102840607-T-C is Benign according to our data. Variant chr11-102840607-T-C is described in ClinVar as Benign. ClinVar VariationId is 403095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002422.5. 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
	MMP3	NM_002422.5	MANE Select	c.626-14A>G		intron	N/A	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.626-14A>G		intron	N/A	ENSP00000299855.5	P08254

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86588

AN:

151908

Hom.:

25173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.585

Gnomad AMR

AF:

0.636

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.675

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.554

GnomAD2 exomes

AF:

0.579

AC:

144750

AN:

249956

AF XY:

0.576

show subpopulations

Gnomad AFR exome

AF:

0.634

Gnomad AMR exome

AF:

0.701

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.667

Gnomad FIN exome

AF:

0.590

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.552

GnomAD4 exome

AF:

0.521

AC:

759735

AN:

1459086

Hom.:

201738

Cov.:

AF XY:

0.526

AC XY:

381501

AN XY:

725928

show subpopulations

African (AFR)

AF:

0.639

AC:

21315

AN:

33334

American (AMR)

AF:

0.693

AC:

30712

AN:

44300

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

15894

AN:

26088

East Asian (EAS)

AF:

0.682

AC:

27050

AN:

39682

South Asian (SAS)

AF:

0.674

AC:

57963

AN:

86004

European-Finnish (FIN)

AF:

0.585

AC:

31230

AN:

53380

Middle Eastern (MID)

AF:

0.613

AC:

3449

AN:

5624

European-Non Finnish (NFE)

AF:

0.486

AC:

539407

AN:

1110384

Other (OTH)

AF:

0.543

AC:

32715

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

17586

35173

52759

70346

87932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16106

32212

48318

64424

80530

<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:

0.570

AC:

86681

AN:

152024

Hom.:

25211

Cov.:

AF XY:

0.579

AC XY:

43021

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.634

AC:

26291

AN:

41466

American (AMR)

AF:

0.636

AC:

9716

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

2132

AN:

3468

East Asian (EAS)

AF:

0.675

AC:

3486

AN:

5166

South Asian (SAS)

AF:

0.697

AC:

3359

AN:

4816

European-Finnish (FIN)

AF:

0.606

AC:

6403

AN:

10558

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.492

AC:

33425

AN:

67956

Other (OTH)

AF:

0.554

AC:

1171

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1859

3719

5578

7438

9297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.533

Hom.:

7916

Bravo

AF:

0.574

Asia WGS

AF:

0.665

AC:

2313

AN:

3478

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

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.5

(source)

DANN

Benign

0.60

PhyloP100

-0.99

Mutation Taster

=100/0

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

Publications

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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