11-102842889-T-C

Position:

chr11-102842889-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000299855.10(MMP3):c.133A>G(p.Lys45Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,608,044 control chromosomes in the GnomAD database, including 227,326 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.58 ( 25701 hom., cov: 31)

Exomes 𝑓: 0.52 ( 201625 hom. )

Consequence

MMP3
ENST00000299855.10 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.176

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.954977E-6).

BP6

Variant 11-102842889-T-C is Benign according to our data. Variant chr11-102842889-T-C is described in ClinVar as [Benign]. Clinvar id is 403098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.133A>G	p.Lys45Glu	missense_variant	2/10	ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10 linkuse as main transcript	c.133A>G	p.Lys45Glu	missense_variant	2/10	1	NM_002422.5	ENSP00000299855	P1
MMP3	ENST00000524478.1 linkuse as main transcript	c.104A>G	p.Gln35Arg	missense_variant, NMD_transcript_variant	2/4	4		ENSP00000435255

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87307

AN:

151766

Hom.:

25663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.653

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.559

GnomAD3 exomes

AF:

0.580

AC:

142818

AN:

246160

Hom.:

42358

AF XY:

0.576

AC XY:

76667

AN XY:

133034

show subpopulations

Gnomad AFR exome

AF:

0.653

Gnomad AMR exome

AF:

0.703

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:

0.490

Gnomad OTH exome

AF:

0.551

GnomAD4 exome

AF:

0.521

AC:

758719

AN:

1456160

Hom.:

201625

Cov.:

AF XY:

0.526

AC XY:

380836

AN XY:

724274

show subpopulations

Gnomad4 AFR exome

AF:

0.659

Gnomad4 AMR exome

AF:

0.695

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:

0.544

GnomAD4 genome

AF:

0.575

AC:

87403

AN:

151884

Hom.:

25701

Cov.:

AF XY:

0.584

AC XY:

43358

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.654

Gnomad4 AMR

AF:

0.639

Gnomad4 ASJ

AF:

0.614

Gnomad4 EAS

AF:

0.673

Gnomad4 SAS

AF:

0.697

Gnomad4 FIN

AF:

0.605

Gnomad4 NFE

AF:

0.492

Gnomad4 OTH

AF:

0.560

Alfa

AF:

0.518

Hom.:

24878

Bravo

AF:

0.581

TwinsUK

AF:

0.482

AC:

1787

ALSPAC

AF:

0.494

AC:

1904

ESP6500AA

AF:

0.639

AC:

2815

ESP6500EA

AF:

0.500

AC:

4301

ExAC

AF:

0.570

AC:

69190

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	This variant is associated with the following publications: (PMID: 26771213, 19008710, 19406964, 25525159, 19551141, 21753786) -

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

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.22

DANN

Benign

0.28

DEOGEN2

Benign

0.11

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.0030

MetaRNN

Benign

0.0000020

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.090

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.020

REVEL

Benign

0.0070

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.036

MPC

0.017

ClinPred

0.00055

GERP RS

-0.22

Varity_R

0.12

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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