chr20-46009039-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004994.3(MMP9):c.113A>G(p.Asn38Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,613,776 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 16 hom., cov: 31)

Exomes 𝑓: 0.011 ( 122 hom. )

Consequence

MMP9
NM_004994.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.00100

Publications

18 publications found

Variant links:

Genes affected

MMP9 (HGNC:7176): (matrix metallopeptidase 9) 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. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling. [provided by RefSeq, Jul 2008]

MMP9 Gene-Disease associations (from GenCC):

metaphyseal anadysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
metaphyseal anadysplasia 2
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MMP9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003079921).

BP6

Variant 20-46009039-A-G is Benign according to our data. Variant chr20-46009039-A-G is described in ClinVar as Benign. ClinVar VariationId is 708035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1621 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3 link	c.113A>G	p.Asn38Ser	missense_variant	Exon 1 of 13	ENST00000372330.3	NP_004985.2	P14780

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3 link	c.113A>G	p.Asn38Ser	missense_variant	Exon 1 of 13	1	NM_004994.3	ENSP00000361405.3		P14780

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1621

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.0516

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00498

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00928

AC:

2324

AN:

250452

AF XY:

0.00923

show subpopulations

Gnomad AFR exome

AF:

0.00911

Gnomad AMR exome

AF:

0.00611

Gnomad ASJ exome

AF:

0.0473

Gnomad EAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.00312

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0114

AC:

16648

AN:

1461594

Hom.:

122

Cov.:

AF XY:

0.0112

AC XY:

8124

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.00983

AC:

329

AN:

33468

American (AMR)

AF:

0.00647

AC:

289

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0501

AC:

1309

AN:

26120

East Asian (EAS)

AF:

0.000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.00385

AC:

332

AN:

86188

European-Finnish (FIN)

AF:

0.00324

AC:

173

AN:

53400

Middle Eastern (MID)

AF:

0.00780

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0120

AC:

13290

AN:

1111884

Other (OTH)

AF:

0.0141

AC:

851

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

1022

2044

3065

4087

5109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.0107

AC:

1621

AN:

152182

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

768

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0106

AC:

441

AN:

41498

American (AMR)

AF:

0.00745

AC:

114

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

177

AN:

3468

East Asian (EAS)

AF:

0.00116

AC:

AN:

5166

South Asian (SAS)

AF:

0.00519

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0111

AC:

756

AN:

68014

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0123

Hom.:

Bravo

AF:

0.0117

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.0120

AC:

103

ExAC

AF:

0.00878

AC:

1066

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.0128

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 16, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22942228, 24627221) -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MMP9: BP4, BS1, BS2 -

Metaphyseal anadysplasia 2

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.2

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.13

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.4

PhyloP100

-0.0010

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.83

REVEL

Benign

0.033

Sift

Benign

0.58

Sift4G

Benign

0.64

Polyphen

0.011

Vest4

0.17

MVP

0.34

ClinPred

0.0091

GERP RS

-3.1

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.11

gMVP

0.58

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over