Genetic Variant MMP3:p.Ala362Ala (chr11-102838694-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_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

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-102838694-A-G is Benign according to our data. Variant chr11-102838694-A-G is described in ClinVar as [Benign]. Clinvar id 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	P08254

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		P08254
MMP3	ENST00000434103.1 link	c.15T>C	p.Ala5Ala	synonymous_variant	Exon 1 of 3	3		ENSP00000398346.1		H7C139

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

GnomAD3 exomes

AF:

0.574

AC:

143760

AN:

250526

Hom.:

42373

AF XY:

0.572

AC XY:

77466

AN XY:

135444

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 SAS exome

AF:

0.675

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

Gnomad4 AFR exome

AF:

0.552

Gnomad4 AMR exome

AF:

0.689

Gnomad4 ASJ exome

AF:

0.608

Gnomad4 EAS exome

AF:

0.682

Gnomad4 SAS exome

AF:

0.675

Gnomad4 FIN exome

AF:

0.595

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.537

GnomAD4 genome

AF:

0.548

AC:

83166

AN:

151878

Hom.:

23209

Cov.:

AF XY:

0.557

AC XY:

41353

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.553

Gnomad4 AMR

AF:

0.629

Gnomad4 ASJ

AF:

0.614

Gnomad4 EAS

AF:

0.677

Gnomad4 SAS

AF:

0.698

Gnomad4 FIN

AF:

0.620

Gnomad4 NFE

AF:

0.491

Gnomad4 OTH

AF:

0.539

Alfa

AF:

0.512

Hom.:

9324

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

DANN

Benign

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over