Variant chr22-23779191-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005940.5(MMP11):c.113C>T(p.Ala38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 1,590,512 control chromosomes in the GnomAD database, including 622,731 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.80 ( 50485 hom., cov: 32)

Exomes 𝑓: 0.89 ( 572246 hom. )

Consequence

MMP11
NM_005940.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.355

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1547959E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP11	NM_005940.5 linkuse as main transcript	c.113C>T	p.Ala38Val	missense_variant	2/8	ENST00000215743.8	NP_005931.2
MMP11	NR_133013.2 linkuse as main transcript	n.135C>T		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP11	ENST00000215743.8 linkuse as main transcript	c.113C>T	p.Ala38Val	missense_variant	2/8	1	NM_005940.5	ENSP00000215743	P1

Frequencies

GnomAD3 genomes

AF:

0.801

AC:

121792

AN:

151986

Hom.:

50491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.851

Gnomad ASJ

AF:

0.875

Gnomad EAS

AF:

0.697

Gnomad SAS

AF:

0.707

Gnomad FIN

AF:

0.938

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.917

Gnomad OTH

AF:

0.816

GnomAD3 exomes

AF:

0.838

AC:

179153

AN:

213824

Hom.:

76325

AF XY:

0.841

AC XY:

97903

AN XY:

116400

show subpopulations

Gnomad AFR exome

AF:

0.552

Gnomad AMR exome

AF:

0.821

Gnomad ASJ exome

AF:

0.868

Gnomad EAS exome

AF:

0.695

Gnomad SAS exome

AF:

0.733

Gnomad FIN exome

AF:

0.936

Gnomad NFE exome

AF:

0.918

Gnomad OTH exome

AF:

0.862

GnomAD4 exome

AF:

0.888

AC:

1277517

AN:

1438408

Hom.:

572246

Cov.:

AF XY:

0.885

AC XY:

631626

AN XY:

713842

show subpopulations

Gnomad4 AFR exome

AF:

0.557

Gnomad4 AMR exome

AF:

0.826

Gnomad4 ASJ exome

AF:

0.867

Gnomad4 EAS exome

AF:

0.663

Gnomad4 SAS exome

AF:

0.738

Gnomad4 FIN exome

AF:

0.935

Gnomad4 NFE exome

AF:

0.920

Gnomad4 OTH exome

AF:

0.865

GnomAD4 genome

AF:

0.801

AC:

121811

AN:

152104

Hom.:

50485

Cov.:

AF XY:

0.801

AC XY:

59553

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.573

Gnomad4 AMR

AF:

0.850

Gnomad4 ASJ

AF:

0.875

Gnomad4 EAS

AF:

0.697

Gnomad4 SAS

AF:

0.706

Gnomad4 FIN

AF:

0.938

Gnomad4 NFE

AF:

0.917

Gnomad4 OTH

AF:

0.807

Alfa

AF:

0.895

Hom.:

119902

Bravo

AF:

0.786

TwinsUK

AF:

0.929

AC:

3444

ALSPAC

AF:

0.921

AC:

3549

ESP6500AA

AF:

0.580

AC:

2539

ESP6500EA

AF:

0.916

AC:

7867

ExAC

AF:

0.822

AC:

98276

Asia WGS

AF:

0.688

AC:

2391

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.0

DANN

Benign

0.92

DEOGEN2

Benign

0.055

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.080

MetaRNN

Benign

0.0000012

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.27

REVEL

Benign

0.062

Sift

Benign

0.33

Sift4G

Benign

0.57

Polyphen

0.099

Vest4

0.068

MPC

0.32

ClinPred

0.0031

GERP RS

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.031

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over