Genetic Variant MMP9:c.-155_-154insCACA (chr20-46008772-C-CCACA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004994.3(MMP9):c.-155_-154insCACA variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 996,250 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

MMP9
NM_004994.3 upstream_gene

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.112

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3 link	c.-155_-154insCACA		upstream_gene_variant		ENST00000372330.3	NP_004985.2	P14780

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3 link	c.-155_-154insCACA		upstream_gene_variant		1	NM_004994.3	ENSP00000361405.3		P14780

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

186

AN:

141530

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00146

Gnomad AMI

AF:

0.0167

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00207

Gnomad SAS

AF:

0.000716

Gnomad FIN

AF:

0.000325

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000910

Gnomad OTH

AF:

0.00105

GnomAD4 exome

AF:

0.000522

AC:

446

AN:

854618

Hom.:

AF XY:

0.000531

AC XY:

231

AN XY:

435276

show subpopulations

Gnomad4 AFR exome

AF:

0.000686

Gnomad4 AMR exome

AF:

0.000853

Gnomad4 ASJ exome

AF:

0.000102

Gnomad4 EAS exome

AF:

0.00224

Gnomad4 SAS exome

AF:

0.000866

Gnomad4 FIN exome

AF:

0.000732

Gnomad4 NFE exome

AF:

0.000387

Gnomad4 OTH exome

AF:

0.000597

GnomAD4 genome

AF:

0.00131

AC:

186

AN:

141632

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

AN XY:

68288

show subpopulations

Gnomad4 AFR

AF:

0.00145

Gnomad4 AMR

AF:

0.00280

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00207

Gnomad4 SAS

AF:

0.000717

Gnomad4 FIN

AF:

0.000325

Gnomad4 NFE

AF:

0.000910

Gnomad4 OTH

AF:

0.00104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

20-46008772-CCACACACACACACACACACACACACACACACACA-CCACACACACACACACACACACACACACACACACACACA

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