20-46011586-A-G

Variant names:

Variant summary

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

The NM_004994.3(MMP9):c.836A>G(p.Gln279Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,613,158 control chromosomes in the GnomAD database, including 115,296 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10759 hom., cov: 31)

Exomes 𝑓: 0.37 ( 104537 hom. )

Consequence

MMP9
NM_004994.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.23

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 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=1.4534767E-6).

BP6

Variant 20-46011586-A-G is Benign according to our data. Variant chr20-46011586-A-G is described in ClinVar as [Benign]. Clinvar id is 338550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3 link	c.836A>G	p.Gln279Arg	missense_variant	Exon 6 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.836A>G	p.Gln279Arg	missense_variant	Exon 6 of 13	1	NM_004994.3	ENSP00000361405.3		P14780

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55636

AN:

151328

Hom.:

10757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.727

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.358

GnomAD3 exomes

AF:

0.389

AC:

97838

AN:

251348

Hom.:

21077

AF XY:

0.399

AC XY:

54201

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.342

Gnomad AMR exome

AF:

0.225

Gnomad ASJ exome

AF:

0.395

Gnomad EAS exome

AF:

0.745

Gnomad SAS exome

AF:

0.502

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.371

AC:

542171

AN:

1461712

Hom.:

104537

Cov.:

AF XY:

0.375

AC XY:

272672

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.351

Gnomad4 AMR exome

AF:

0.229

Gnomad4 ASJ exome

AF:

0.394

Gnomad4 EAS exome

AF:

0.696

Gnomad4 SAS exome

AF:

0.497

Gnomad4 FIN exome

AF:

0.407

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.368

AC:

55669

AN:

151446

Hom.:

10759

Cov.:

AF XY:

0.375

AC XY:

27731

AN XY:

74018

show subpopulations

Gnomad4 AFR

AF:

0.345

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.726

Gnomad4 SAS

AF:

0.519

Gnomad4 FIN

AF:

0.418

Gnomad4 NFE

AF:

0.357

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.355

Hom.:

18400

Bravo

AF:

0.355

TwinsUK

AF:

0.355

AC:

1317

ALSPAC

AF:

0.358

AC:

1381

ESP6500AA

AF:

0.348

AC:

1533

ESP6500EA

AF:

0.348

AC:

2991

ExAC

AF:

0.392

AC:

47586

Asia WGS

AF:

0.553

AC:

1920

AN:

3478

EpiCase

AF:

0.350

EpiControl

AF:

0.347

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20181264, 18455130, 20144500, 21844877, 19279308, 21655354, 16709939, 28453874, 21085059) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Metaphyseal anadysplasia 2

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.063

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0000015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.50

REVEL

Benign

0.033

Sift

Benign

0.35

Sift4G

Benign

0.29

Polyphen

0.0040

Vest4

0.055

ClinPred

0.0035

GERP RS

2.7

Varity_R

0.073

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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