rs520540

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002422.5(MMP3):c.1086T>C(p.Ala362Ala) 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 1,611,212 control chromosomes in the GnomAD database, including 223,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23209 hom., cov: 32)

Exomes 𝑓: 0.52 ( 200076 hom. )

Consequence

MMP3
NM_002422.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.523

Publications

58 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.072).

BP6

Variant 11-102838694-A-G is Benign according to our data. Variant chr11-102838694-A-G is described in ClinVar as Benign. ClinVar VariationId is 403094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.523 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5 link	c.1086T>C	p.Ala362Ala	synonymous_variant	Exon 8 of 10	ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10 link	c.1086T>C	p.Ala362Ala	synonymous_variant	Exon 8 of 10	1	NM_002422.5	ENSP00000299855.5
MMP3	ENST00000434103.1 link	c.15T>C	p.Ala5Ala	synonymous_variant	Exon 1 of 3	3		ENSP00000398346.1

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83082

AN:

151760

Hom.:

23176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.553

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.678

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.538

GnomAD2 exomes

AF:

0.574

AC:

143760

AN:

250526

AF XY:

0.572

show subpopulations

Gnomad AFR exome

AF:

0.550

Gnomad AMR exome

AF:

0.698

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.668

Gnomad FIN exome

AF:

0.602

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.551

GnomAD4 exome

AF:

0.518

AC:

756308

AN:

1459334

Hom.:

200076

Cov.:

AF XY:

0.523

AC XY:

380117

AN XY:

726138

show subpopulations

African (AFR)

AF:

0.552

AC:

18439

AN:

33390

American (AMR)

AF:

0.689

AC:

30686

AN:

44542

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

15863

AN:

26084

East Asian (EAS)

AF:

0.682

AC:

27077

AN:

39692

South Asian (SAS)

AF:

0.675

AC:

58097

AN:

86118

European-Finnish (FIN)

AF:

0.595

AC:

31740

AN:

53334

Middle Eastern (MID)

AF:

0.610

AC:

3513

AN:

5758

European-Non Finnish (NFE)

AF:

0.485

AC:

538513

AN:

1110106

Other (OTH)

AF:

0.537

AC:

32380

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

16670

33340

50009

66679

83349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16062

32124

48186

64248

80310

<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:

0.548

AC:

83166

AN:

151878

Hom.:

23209

Cov.:

AF XY:

0.557

AC XY:

41353

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.553

AC:

22934

AN:

41444

American (AMR)

AF:

0.629

AC:

9597

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

2132

AN:

3470

East Asian (EAS)

AF:

0.677

AC:

3494

AN:

5158

South Asian (SAS)

AF:

0.698

AC:

3347

AN:

4792

European-Finnish (FIN)

AF:

0.620

AC:

6490

AN:

10474

Middle Eastern (MID)

AF:

0.572

AC:

167

AN:

292

European-Non Finnish (NFE)

AF:

0.491

AC:

33340

AN:

67968

Other (OTH)

AF:

0.539

AC:

1136

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1892

3784

5675

7567

9459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.512

Hom.:

9425

Bravo

AF:

0.547

Asia WGS

AF:

0.663

AC:

2304

AN:

3478

EpiCase

AF:

0.498

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.52

PromoterAI

0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over