11-102842734-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002422.5(MMP3):c.288T>C(p.Asp96=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.36

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP3	NM_002422.5	c.288T>C	p.Asp96=	synonymous_variant	2/10	ENST00000299855.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP3	ENST00000299855.10	c.288T>C	p.Asp96=	synonymous_variant	2/10	1	NM_002422.5	P1
MMP3	ENST00000524478.1	c.*130T>C		3_prime_UTR_variant, NMD_transcript_variant	2/4	4

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82732 AN: 151746 Hom.: 22910 Cov.: 31

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

GnomAD3 exomes AF: 0.573 AC: 143688 AN: 250880 Hom.: 42158 AF XY: 0.571 AC XY: 77413 AN XY: 135570

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 SAS exome AF: 0.674

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.: 64 AF XY: 0.523 AC XY: 380508 AN XY: 727052

Gnomad4 AFR exome AF: 0.548

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.609

Gnomad4 EAS exome AF: 0.679

Gnomad4 SAS exome AF: 0.674

Gnomad4 FIN exome AF: 0.584

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.545 AC: 82815 AN: 151864 Hom.: 22942 Cov.: 31 AF XY: 0.555 AC XY: 41148 AN XY: 74194

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.539

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.036
Dann	Benign	0.28

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

LitVar

Other links and lift over

dbSNP: rs602128; hg19: chr11-102713465; COSMIC: COSV55406163; COSMIC: COSV55406163;