rs41427445

Positions:

chr20-46009039-A-G

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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 -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 id is 708035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46009039-A-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP9	NM_004994.3 linkuse as main transcript	c.113A>G	p.Asn38Ser	missense_variant	1/13	ENST00000372330.3	NP_004985.2	P14780

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3 linkuse as main transcript	c.113A>G	p.Asn38Ser	missense_variant	1/13	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

GnomAD3 exomes

AF:

0.00928

AC:

2324

AN:

250452

Hom.:

AF XY:

0.00923

AC XY:

1250

AN XY:

135402

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 SAS exome

AF:

0.00419

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

Gnomad4 AFR exome

AF:

0.00983

Gnomad4 AMR exome

AF:

0.00647

Gnomad4 ASJ exome

AF:

0.0501

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.00385

Gnomad4 FIN exome

AF:

0.00324

Gnomad4 NFE exome

AF:

0.0120

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.0107

AC:

1621

AN:

152182

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

768

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0106

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.0510

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00519

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0127

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

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	MMP9: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 16, 2021	This variant is associated with the following publications: (PMID: 22942228, 24627221) -

Metaphyseal anadysplasia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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

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

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

Varity_R

0.11

gMVP

0.58

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