11-102842734-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002422.5(MMP3):c.288T>C(p.Asp96Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,613,446 control chromosomes in the GnomAD database, including 222,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 22942 hom., cov: 31)

Exomes 𝑓: 0.52 ( 199729 hom. )

Consequence

MMP3
NM_002422.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.36

Publications

52 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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 11-102842734-A-G is Benign according to our data. Variant chr11-102842734-A-G is described in ClinVar as Benign. ClinVar VariationId is 403097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP3	NM_002422.5	MANE Select	c.288T>C	p.Asp96Asp	synonymous	Exon 2 of 10	NP_002413.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MMP3	ENST00000299855.10	TSL:1 MANE Select	c.288T>C	p.Asp96Asp	synonymous	Exon 2 of 10	ENSP00000299855.5
MMP3	ENST00000524478.1	TSL:4	n.*130T>C		non_coding_transcript_exon	Exon 2 of 4	ENSP00000435255.1
MMP3	ENST00000524478.1	TSL:4	n.*130T>C		3_prime_UTR	Exon 2 of 4	ENSP00000435255.1

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82732

AN:

151746

Hom.:

22910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.538

GnomAD2 exomes

AF:

0.573

AC:

143688

AN:

250880

AF XY:

0.571

show subpopulations

Gnomad AFR exome

AF:

0.546

Gnomad AMR exome

AF:

0.699

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.666

Gnomad FIN exome

AF:

0.589

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.551

GnomAD4 exome

AF:

0.518

AC:

757194

AN:

1461582

Hom.:

199729

Cov.:

AF XY:

0.523

AC XY:

380508

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.548

AC:

18337

AN:

33468

American (AMR)

AF:

0.690

AC:

30825

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

15918

AN:

26132

East Asian (EAS)

AF:

0.679

AC:

26957

AN:

39692

South Asian (SAS)

AF:

0.674

AC:

58105

AN:

86254

European-Finnish (FIN)

AF:

0.584

AC:

31203

AN:

53396

Middle Eastern (MID)

AF:

0.610

AC:

3515

AN:

5766

European-Non Finnish (NFE)

AF:

0.486

AC:

539927

AN:

1111838

Other (OTH)

AF:

0.537

AC:

32407

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

23022

46044

69066

92088

115110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16114

32228

48342

64456

80570

<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:

0.545

AC:

82815

AN:

151864

Hom.:

22942

Cov.:

AF XY:

0.555

AC XY:

41148

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.548

AC:

22704

AN:

41406

American (AMR)

AF:

0.628

AC:

9579

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

2133

AN:

3468

East Asian (EAS)

AF:

0.674

AC:

3464

AN:

5142

South Asian (SAS)

AF:

0.697

AC:

3352

AN:

4812

European-Finnish (FIN)

AF:

0.606

AC:

6383

AN:

10530

Middle Eastern (MID)

AF:

0.572

AC:

167

AN:

292

European-Non Finnish (NFE)

AF:

0.491

AC:

33373

AN:

67950

Other (OTH)

AF:

0.539

AC:

1129

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1872

3744

5617

7489

9361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.484

Hom.:

7114

Bravo

AF:

0.546

Asia WGS

AF:

0.660

AC:

2294

AN:

3478

EpiCase

AF:

0.499

EpiControl

AF:

0.500

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.036

(source)

DANN

Benign

0.28

PhyloP100

-2.4

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over