NM_022468.5:c.318C>A

Variant names:

• chr16-3050094-C-A
• NM_022468.5:c.318C>A
• MMP25 p.Arg106Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_022468.5(MMP25):​c.318C>A​(p.Arg106Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MMP25 NM_022468.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354
• Publications: 0 publications found

Genes affected

MMP25 (HGNC:14246): (matrix metallopeptidase 25) 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 MMPs are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily, attached to the plasma membrane via a glycosylphosphatidyl inositol anchor. In response to bacterial infection or inflammation, the encoded protein is thought to inactivate alpha-1 proteinase inhibitor, a major tissue protectant against proteolytic enzymes released by activated neutrophils, facilitating the transendothelial migration of neutrophils to inflammatory sites. The encoded protein may also play a role in tumor invasion and metastasis through activation of MMP2. The gene has previously been referred to as MMP20 but has been renamed MMP25. [provided by RefSeq, Jul 2008]

MMP25-AS1 (HGNC:51372): (MMP25 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=0.354 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022468.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP25	NM_022468.5	MANE Select	c.318C>A	p.Arg106Arg	synonymous	Exon 3 of 10	NP_071913.1	Q9NPA2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP25	ENST00000336577.9	TSL:1 MANE Select	c.318C>A	p.Arg106Arg	synonymous	Exon 3 of 10	ENSP00000337816.4	Q9NPA2
	MMP25	ENST00000850602.1		c.318C>A	p.Arg106Arg	synonymous	Exon 3 of 10	ENSP00000520889.1	Q9NPA2
	MMP25	ENST00000928201.1		c.303C>A	p.Arg101Arg	synonymous	Exon 3 of 10	ENSP00000598260.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-3100095;