Genetic Variant NM_022468.5:c.85G>T (chr16-3047002-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022468.5(MMP25):c.85G>T(p.Val29Leu) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V29M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MMP25
NM_022468.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.285

Publications

0 publications found

Variant links:

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 links:

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

MMP25-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08280942).

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.85G>T	p.Val29Leu	missense	Exon 1 of 10	NP_071913.1	Q9NPA2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP25	ENST00000336577.9	TSL:1 MANE Select	c.85G>T	p.Val29Leu	missense	Exon 1 of 10	ENSP00000337816.4	Q9NPA2
MMP25	ENST00000850602.1		c.85G>T	p.Val29Leu	missense	Exon 1 of 10	ENSP00000520889.1	Q9NPA2
MMP25	ENST00000928200.1		c.85G>T	p.Val29Leu	missense	Exon 1 of 10	ENSP00000598259.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1311700

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

644806

African (AFR)

AF:

0.00

AC:

AN:

26184

American (AMR)

AF:

0.00

AC:

AN:

23634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22682

East Asian (EAS)

AF:

0.00

AC:

AN:

29036

South Asian (SAS)

AF:

0.00

AC:

AN:

71506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32646

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4056

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047608

Other (OTH)

AF:

0.00

AC:

AN:

54348

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000387

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.047

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.36

M_CAP

Benign

0.0094

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.23

PhyloP100

-0.28

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.33

REVEL

Benign

0.068

Sift

Benign

1.0

Sift4G

Benign

0.91

Polyphen

0.0030

Vest4

0.14

MutPred

0.74

Gain of disorder (P = 0.074)

MVP

0.51

MPC

0.16

ClinPred

0.34

GERP RS

1.1

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.041

gMVP

0.49

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over