20-35226962-C-T

Variant names:

Variant summary

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

The NM_006690.4(MMP24):c.224C>T(p.Ala75Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 979,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A75T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MMP24
NM_006690.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0570

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:

Genome browser will be placed here

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=0.068798125).

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.224C>T	p.Ala75Val	missense	Exon 1 of 9	NP_006681.1	Q9Y5R2
	MMP24-AS1-EDEM2	NM_001355008.2		c.-351-8901G>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.224C>T	p.Ala75Val	missense	Exon 1 of 9	ENSP00000246186.6	Q9Y5R2
MMP24	ENST00000927316.1		c.224C>T	p.Ala75Val	missense	Exon 1 of 8	ENSP00000597375.1
MMP24	ENST00000927315.1		c.224C>T	p.Ala75Val	missense	Exon 1 of 8	ENSP00000597374.1

Frequencies

GnomAD3 genomes

AF:

0.0000344

AC:

AN:

145344

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000986

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000132

AC:

AN:

834486

Hom.:

Cov.:

AF XY:

0.00000778

AC XY:

AN XY:

385524

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15792

American (AMR)

AF:

0.00

AC:

AN:

1008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5160

East Asian (EAS)

AF:

0.00

AC:

AN:

3648

South Asian (SAS)

AF:

0.00

AC:

AN:

17304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1626

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

762326

Other (OTH)

AF:

0.0000366

AC:

AN:

27332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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

AF:

0.0000344

AC:

AN:

145344

Hom.:

Cov.:

AF XY:

0.0000425

AC XY:

AN XY:

70654

show subpopulations

African (AFR)

AF:

0.0000986

AC:

AN:

40564

American (AMR)

AF:

0.00

AC:

AN:

14674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.00

AC:

AN:

4966

South Asian (SAS)

AF:

0.00

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

65548

Other (OTH)

AF:

0.00

AC:

AN:

2004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

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

0.094

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.087

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.35

M_CAP

Benign

0.032

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.057

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.62

REVEL

Benign

0.0040

Sift

Benign

0.20

Sift4G

Uncertain

0.055

Polyphen

0.015

Vest4

0.058

MutPred

0.38

Gain of helix (P = 0.0078)

MVP

0.48

MPC

0.54

ClinPred

0.077

GERP RS

-0.10

PromoterAI

0.016

Neutral

(source)

Varity_R

0.047

gMVP

0.28

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over