Genetic Variant MMP24:p.Pro47Leu (chr20-35226878-C-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_006690.4(MMP24):c.140C>T(p.Pro47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 835,560 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

MMP24
NM_006690.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0220

Publications

0 publications found

Variant links:

Genes affected

MMP24 (HGNC:7172): (matrix metallopeptidase 24) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this 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. The encoded preproprotein is proteolytically processed to generate the mature protease. Unlike most MMPs, which are secreted, this protease is a member of the membrane-type MMP (MT-MMP) subfamily, contains a transmembrane domain and is expressed at the cell surface. Substrates of this protease include the proteins cadherin 2 and matrix metallopeptidase 2 (also known as 72 kDa type IV collagenase). The gene has previously been referred to as MMP25 but has been renamed matrix metallopeptidase 24 (MMP24). [provided by RefSeq, Oct 2019]

MMP24 links:

MMP24-AS1-EDEM2 (HGNC:):

MMP24-AS1-EDEM2 links:

MMP24OS (HGNC:44421): (MMP24 opposite strand)

MMP24OS 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=0.17518222).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006690.4. 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
	MMP24	NM_006690.4	MANE Select	c.140C>T	p.Pro47Leu	missense	Exon 1 of 9	NP_006681.1	Q9Y5R2
	MMP24-AS1-EDEM2	NM_001355008.2		c.-351-8817G>A		intron	N/A	NP_001341937.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP24	ENST00000246186.8	TSL:1 MANE Select	c.140C>T	p.Pro47Leu	missense	Exon 1 of 9	ENSP00000246186.6	Q9Y5R2
MMP24	ENST00000927316.1		c.140C>T	p.Pro47Leu	missense	Exon 1 of 8	ENSP00000597375.1
MMP24	ENST00000927315.1		c.140C>T	p.Pro47Leu	missense	Exon 1 of 8	ENSP00000597374.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000120

AC:

AN:

835560

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

386342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15826

American (AMR)

AF:

0.00

AC:

AN:

1008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5162

East Asian (EAS)

AF:

0.00

AC:

AN:

3708

South Asian (SAS)

AF:

0.00

AC:

AN:

17310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1626

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

763290

Other (OTH)

AF:

0.00

AC:

AN:

27342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.034

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.36

M_CAP

Benign

0.011

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.022

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.13

REVEL

Benign

0.12

Sift

Benign

0.15

Sift4G

Benign

0.16

Polyphen

0.98

Vest4

0.097

MutPred

0.42

Loss of loop (P = 9e-04)

MVP

0.58

MPC

0.55

ClinPred

0.23

PromoterAI

0.029

Neutral

(source)

Varity_R

0.060

gMVP

0.22

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over