Variant 11-102842734-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).

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	Protein	UniProt
MMP3	NM_002422.5 linkuse as main transcript	c.288T>C	p.Asp96Asp	synonymous_variant	2/10	ENST00000299855.10	NP_002413.1	P08254

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MMP3	ENST00000299855.10 linkuse as main transcript	c.288T>C	p.Asp96Asp	synonymous_variant	2/10	1	NM_002422.5	ENSP00000299855.5	P08254
MMP3	ENST00000524478.1 linkuse as main transcript	n.*130T>C		non_coding_transcript_exon_variant	2/4	4		ENSP00000435255.1	E9PKX2
MMP3	ENST00000524478.1 linkuse as main transcript	n.*130T>C		3_prime_UTR_variant	2/4	4		ENSP00000435255.1	E9PKX2

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

GnomAD3 exomes

AF:

0.573

AC:

143688

AN:

250880

Hom.:

42158

AF XY:

0.571

AC XY:

77413

AN XY:

135570

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 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.:

AF XY:

0.523

AC XY:

380508

AN XY:

727052

show subpopulations

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.:

AF XY:

0.555

AC XY:

41148

AN XY:

74194

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

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 -

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

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