20-35226791-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.53C>T(p.Pro18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000948 in 738,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

MMP24
NM_006690.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0230

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=0.0672223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP24	NM_006690.4 link	c.53C>T	p.Pro18Leu	missense_variant	Exon 1 of 9	ENST00000246186.8	NP_006681.1	Q9Y5R2Q86VV6
MMP24	XM_017027597.2 link	c.53C>T	p.Pro18Leu	missense_variant	Exon 1 of 8		XP_016883086.1
MMP24	XM_011528500.3 link	c.53C>T	p.Pro18Leu	missense_variant	Exon 1 of 8		XP_011526802.1
MMP24-AS1-EDEM2	NM_001355008.2 link	c.-351-8730G>A		intron_variant	Intron 3 of 14		NP_001341937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP24	ENST00000246186.8 link	c.53C>T	p.Pro18Leu	missense_variant	Exon 1 of 9	1	NM_006690.4	ENSP00000246186.6		Q9Y5R2

Frequencies

GnomAD3 genomes

AF:

0.0000229

AC:

AN:

131264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000794

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000659

AC:

AN:

607150

Hom.:

Cov.:

AF XY:

0.00000356

AC XY:

AN XY:

281222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15064

American (AMR)

AF:

0.00

AC:

AN:

712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3994

East Asian (EAS)

AF:

0.000810

AC:

AN:

2468

South Asian (SAS)

AF:

0.00

AC:

AN:

13642

European-Finnish (FIN)

AF:

0.00

AC:

AN:

194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1254

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

549806

Other (OTH)

AF:

0.0000500

AC:

AN:

20016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000229

AC:

AN:

131264

Hom.:

Cov.:

AF XY:

0.0000315

AC XY:

AN XY:

63422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39766

American (AMR)

AF:

0.00

AC:

AN:

12726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3138

East Asian (EAS)

AF:

0.000794

AC:

AN:

3776

South Asian (SAS)

AF:

0.00

AC:

AN:

4200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

252

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

58138

Other (OTH)

AF:

0.00

AC:

AN:

1798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 25, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.53C>T (p.P18L) alteration is located in exon (coding exon ) of the MMP24 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the proline (P) at amino acid position 18 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.048

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00085

LIST_S2

Benign

0.29

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.023

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.0

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.28

MutPred

0.19

Loss of glycosylation at P18 (P = 4e-04);

MVP

0.53

MPC

0.55

ClinPred

0.15

PromoterAI

-0.0094

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.23

Mutation Taster

=99/1

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.

20-35226791-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over