20-46009055-G-T

Position:

• chr20-46009055-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004994.3(MMP9):​c.129G>T​(p.Gln43His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: MMP9 NM_004994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20491484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP9	NM_004994.3	c.129G>T	p.Gln43His	missense_variant	1/13	ENST00000372330.3	NP_004985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3	c.129G>T	p.Gln43His	missense_variant	1/13	1	NM_004994.3	ENSP00000361405.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000801 AC: 2 AN: 249814 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461436 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726990

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.048
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.18	B
Vest4		0.39
MutPred		0.72		Loss of stability (P = 0.1376);
MVP		0.73
ClinPred		0.88	D
GERP RS		3.3
Varity_R		0.62
gMVP		0.61

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

Other links and lift over

dbSNP: rs142807270; hg19: chr20-44637694;