Genetic Variant MMP3:c.1334-409T>A (chr11-102836635-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002422.5(MMP3):c.1334-409T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 460,442 control chromosomes in the GnomAD database, including 4,189 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 1233 hom., cov: 32)

Exomes 𝑓: 0.13 ( 2956 hom. )

Consequence

MMP3
NM_002422.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.115

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:

WTAPP1 (HGNC:44115): (WTAP pseudogene 1)

WTAPP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5 link	c.1334-409T>A		intron_variant	Intron 9 of 9	ENST00000299855.10	NP_002413.1	P08254
WTAPP1	NR_038390.1 link	n.2511A>T		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP3	ENST00000299855.10 link	c.1334-409T>A	intron_variant	Intron 9 of 9	1	NM_002422.5	ENSP00000299855.5	P08254
MMP3	ENST00000434103.1 link	c.263-107T>A	intron_variant	Intron 2 of 2	3		ENSP00000398346.1	H7C139
WTAPP1	ENST00000525739.6 link	n.2511A>T	non_coding_transcript_exon_variant	Exon 8 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15857

AN:

151922

Hom.:

1233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0841

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.0726

Gnomad SAS

AF:

0.0788

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.126

AC:

38926

AN:

308402

Hom.:

2956

Cov.:

AF XY:

0.123

AC XY:

21283

AN XY:

173346

show subpopulations

Gnomad4 AFR exome

AF:

0.0238

AC:

200

AN:

8418

Gnomad4 AMR exome

AF:

0.0738

AC:

1938

AN:

26244

Gnomad4 ASJ exome

AF:

0.131

AC:

1325

AN:

10106

Gnomad4 EAS exome

AF:

0.0803

AC:

735

AN:

9150

Gnomad4 SAS exome

AF:

0.0849

AC:

4866

AN:

57330

Gnomad4 FIN exome

AF:

0.247

AC:

6648

AN:

26876

Gnomad4 NFE exome

AF:

0.137

AC:

21092

AN:

153510

Gnomad4 Remaining exome

AF:

0.124

AC:

1749

AN:

14066

Heterozygous variant carriers

1590

3180

4771

6361

7951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.104

AC:

15857

AN:

152040

Hom.:

1233

Cov.:

AF XY:

0.108

AC XY:

8059

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0246

AC:

0.0246083

AN:

0.0246083

Gnomad4 AMR

AF:

0.0841

AC:

0.0840534

AN:

0.0840534

Gnomad4 ASJ

AF:

0.126

AC:

0.12637

AN:

0.12637

Gnomad4 EAS

AF:

0.0725

AC:

0.0725338

AN:

0.0725338

Gnomad4 SAS

AF:

0.0792

AC:

0.0792429

AN:

0.0792429

Gnomad4 FIN

AF:

0.279

AC:

0.278505

AN:

0.278505

Gnomad4 NFE

AF:

0.133

AC:

0.133371

AN:

0.133371

Gnomad4 OTH

AF:

0.103

AC:

0.102564

AN:

0.102564

Heterozygous variant carriers

672

1344

2015

2687

3359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.124

Hom.:

184

Bravo

AF:

0.0873

Asia WGS

AF:

0.0690

AC:

239

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.1

DANN

Benign

0.75

Mutation Taster

=100/0

polymorphism (auto)

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over