NM_004994.3:c.59C>T

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.59C>T(p.Ala20Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,613,788 control chromosomes in the GnomAD database, including 1,152 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 172 hom., cov: 31)

Exomes 𝑓: 0.026 ( 980 hom. )

Consequence

MMP9
NM_004994.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.15

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017846525).

BP6

Variant 20-46008985-C-T is Benign according to our data. Variant chr20-46008985-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 338546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46008985-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3 link	c.59C>T	p.Ala20Val	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.59C>T	p.Ala20Val	missense_variant	Exon 1 of 13	1	NM_004994.3	ENSP00000361405.3		P14780

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4357

AN:

152050

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00763

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0541

Gnomad EAS

AF:

0.0304

Gnomad SAS

AF:

0.0244

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0210

Gnomad OTH

AF:

0.0320

GnomAD3 exomes

AF:

0.0408

AC:

10234

AN:

250604

Hom.:

525

AF XY:

0.0365

AC XY:

4943

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.00581

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.0513

Gnomad EAS exome

AF:

0.0308

Gnomad SAS exome

AF:

0.0280

Gnomad FIN exome

AF:

0.0216

Gnomad NFE exome

AF:

0.0201

Gnomad OTH exome

AF:

0.0394

GnomAD4 exome

AF:

0.0262

AC:

38315

AN:

1461620

Hom.:

980

Cov.:

AF XY:

0.0259

AC XY:

18822

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00493

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.0534

Gnomad4 EAS exome

AF:

0.0398

Gnomad4 SAS exome

AF:

0.0279

Gnomad4 FIN exome

AF:

0.0193

Gnomad4 NFE exome

AF:

0.0208

Gnomad4 OTH exome

AF:

0.0294

GnomAD4 genome

AF:

0.0287

AC:

4363

AN:

152168

Hom.:

172

Cov.:

AF XY:

0.0307

AC XY:

2286

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00761

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0541

Gnomad4 EAS

AF:

0.0303

Gnomad4 SAS

AF:

0.0249

Gnomad4 FIN

AF:

0.0184

Gnomad4 NFE

AF:

0.0210

Gnomad4 OTH

AF:

0.0322

Alfa

AF:

0.0191

Hom.:

Bravo

AF:

0.0352

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0210

AC:

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.0223

AC:

192

ExAC

AF:

0.0344

AC:

4174

Asia WGS

AF:

0.0290

AC:

100

AN:

3478

EpiCase

AF:

0.0216

EpiControl

AF:

0.0227

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Metaphyseal anadysplasia 2

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.76

REVEL

Benign

0.053

Sift

Benign

0.22

Sift4G

Benign

0.53

Polyphen

0.35

Vest4

0.087

ClinPred

0.0085

GERP RS

2.6

Varity_R

0.038

gMVP

0.51

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