Genetic Variant MMP11:p.Pro63Ser (chr22-23779265-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_005940.5(MMP11):c.187C>T(p.Pro63Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,457,464 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MMP11
NM_005940.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0510

Publications

0 publications found

Variant links:

Genes affected

MMP11 (HGNC:7157): (matrix metallopeptidase 11) Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is activated intracellularly by furin within the constitutive secretory pathway. Also in contrast to other MMP's, this enzyme cleaves alpha 1-proteinase inhibitor but weakly degrades structural proteins of the extracellular matrix. [provided by RefSeq, Jul 2008]

MMP11 links:

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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=0.033762693).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005940.5. 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
	MMP11	NM_005940.5	MANE Select	c.187C>T	p.Pro63Ser	missense	Exon 2 of 8	NP_005931.2	P24347
	MMP11	NR_133013.2		n.209C>T		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP11	ENST00000215743.8	TSL:1 MANE Select	c.187C>T	p.Pro63Ser	missense	Exon 2 of 8	ENSP00000215743.3	P24347
MMP11	ENST00000872484.1		c.187C>T	p.Pro63Ser	missense	Exon 2 of 8	ENSP00000542543.1
MMP11	ENST00000872487.1		c.187C>T	p.Pro63Ser	missense	Exon 2 of 8	ENSP00000542546.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000297

AC:

AN:

235408

AF XY:

0.0000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000400

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457464

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724762

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.00

AC:

AN:

44356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.000202

AC:

AN:

39558

South Asian (SAS)

AF:

0.00

AC:

AN:

85564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110648

Other (OTH)

AF:

0.00

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

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

0.069

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.5

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.095

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.028

M_CAP

Benign

0.0021

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.11

PhyloP100

-0.051

PrimateAI

Benign

0.36

PROVEAN

Benign

0.080

REVEL

Benign

0.0090

Sift

Benign

0.38

Sift4G

Benign

0.28

Polyphen

0.0010

Vest4

0.11

MutPred

0.18

Gain of phosphorylation at P63 (P = 0.0155)

MVP

0.20

MPC

0.32

ClinPred

0.037

GERP RS

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.023

gMVP

0.34

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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