20-35226781-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_006690.4(MMP24):c.43C>T(p.Pro15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.33 ( 3 hom., cov: 0)

Exomes 𝑓: 0.0016 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

MMP24
NM_006690.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.238

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06906623).

BP6

Variant 20-35226781-C-T is Benign according to our data. Variant chr20-35226781-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2362130.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.0016 (252/157094) while in subpopulation AFR AF = 0.0174 (229/13176). AF 95% confidence interval is 0.0155. There are 2 homozygotes in GnomAdExome4. There are 108 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP24	NM_006690.4 link	c.43C>T	p.Pro15Ser	missense_variant	Exon 1 of 9	ENST00000246186.8	NP_006681.1	Q9Y5R2Q86VV6
MMP24	XM_017027597.2 link	c.43C>T	p.Pro15Ser	missense_variant	Exon 1 of 8		XP_016883086.1
MMP24	XM_011528500.3 link	c.43C>T	p.Pro15Ser	missense_variant	Exon 1 of 8		XP_011526802.1
MMP24-AS1-EDEM2	NM_001355008.2 link	c.-351-8720G>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.43C>T	p.Pro15Ser	missense_variant	Exon 1 of 9	1	NM_006690.4	ENSP00000246186.6		Q9Y5R2

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

533

AN:

1594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.243

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:

0.00758

Gnomad OTH

AF:

0.278

GnomAD4 exome

AF:

0.00160

AC:

252

AN:

157094

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

108

AN XY:

72550

show subpopulations

African (AFR)

AF:

0.0174

AC:

229

AN:

13176

American (AMR)

AF:

0.00

AC:

AN:

116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1496

East Asian (EAS)

AF:

0.00

AC:

AN:

432

South Asian (SAS)

AF:

0.000164

AC:

AN:

6116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

490

European-Non Finnish (NFE)

AF:

0.00000771

AC:

AN:

129650

Other (OTH)

AF:

0.00378

AC:

AN:

5558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.334

AC:

533

AN:

1596

Hom.:

Cov.:

AF XY:

0.325

AC XY:

257

AN XY:

790

show subpopulations

African (AFR)

AF:

0.405

AC:

509

AN:

1256

American (AMR)

AF:

0.243

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00758

AC:

AN:

132

Other (OTH)

AF:

0.278

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

May 09, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

0.0047

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.049

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.29

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.0

PhyloP100

0.24

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.29

REVEL

Benign

0.28

Sift

Benign

0.29

Sift4G

Benign

0.10

Polyphen

0.0010

Vest4

0.22

MutPred

0.31

Gain of phosphorylation at P15 (P = 0.0013);

MVP

0.47

MPC

0.55

ClinPred

0.093

GERP RS

-2.9

PromoterAI

0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.039

gMVP

0.27

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

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20-35226781-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