20-35226784-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006690.4(MMP24):c.46C>T(p.Pro16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

MMP24
NM_006690.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.925

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018298805).

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.46C>T	p.Pro16Ser	missense	Exon 1 of 9	NP_006681.1	Q9Y5R2
	MMP24-AS1-EDEM2	NM_001355008.2		c.-351-8723G>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.46C>T	p.Pro16Ser	missense	Exon 1 of 9	ENSP00000246186.6	Q9Y5R2
MMP24	ENST00000927316.1		c.46C>T	p.Pro16Ser	missense	Exon 1 of 8	ENSP00000597375.1
MMP24	ENST00000927315.1		c.46C>T	p.Pro16Ser	missense	Exon 1 of 8	ENSP00000597374.1

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

AN:

1722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00833

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:

0.00147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000255

AC:

AN:

784660

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

362812

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000663

AC:

AN:

15088

American (AMR)

AF:

0.00

AC:

AN:

920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4906

East Asian (EAS)

AF:

0.00

AC:

AN:

3386

South Asian (SAS)

AF:

0.00

AC:

AN:

15706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1518

European-Non Finnish (NFE)

AF:

0.00000139

AC:

AN:

717184

Other (OTH)

AF:

0.00

AC:

AN:

25692

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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:

0.00116

AC:

AN:

1722

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

332

American (AMR)

AF:

0.00833

AC:

AN:

120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

102

South Asian (SAS)

AF:

0.00

AC:

AN:

136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00147

AC:

AN:

680

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.00

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

0.091

BayesDel_addAF

Benign

0.0062

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.046

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.29

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.0

PhyloP100

-0.93

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.40

REVEL

Uncertain

0.34

Sift

Benign

0.81

Sift4G

Benign

0.24

Polyphen

0.91

Vest4

0.26

MutPred

0.26

Gain of phosphorylation at P16 (P = 0.0016)

MVP

0.66

MPC

0.55

ClinPred

0.18

GERP RS

-0.18

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.041

gMVP

0.27

Mutation Taster

=95/5

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over