14-22836839-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004995.4(MMP14):c.22C>T(p.Pro8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,611,232 control chromosomes in the GnomAD database, including 575,345 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 54474 hom., cov: 30)

Exomes 𝑓: 0.84 ( 520871 hom. )

Consequence

MMP14
NM_004995.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.424

Publications

46 publications found

Variant links:

Genes affected

MMP14 (HGNC:7160): (matrix metallopeptidase 14) 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 protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion. [provided by RefSeq, Jul 2008]

MMP14 Gene-Disease associations (from GenCC):

Winchester syndrome
Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
multicentric osteolysis-nodulosis-arthropathy spectrum
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MMP14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.0322017E-7).

BP6

Variant 14-22836839-C-T is Benign according to our data. Variant chr14-22836839-C-T is described in ClinVar as Benign. ClinVar VariationId is 1279198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004995.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP14	NM_004995.4	MANE Select	c.22C>T	p.Pro8Ser	missense	Exon 1 of 10	NP_004986.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MMP14	ENST00000311852.11	TSL:1 MANE Select	c.22C>T	p.Pro8Ser	missense	Exon 1 of 10	ENSP00000308208.6
MMP14	ENST00000548162.2	TSL:5	c.22C>T	p.Pro8Ser	missense	Exon 1 of 10	ENSP00000506068.1
MMP14	ENST00000547074.1	TSL:2	n.280C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.846

AC:

128389

AN:

151806

Hom.:

54425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.830

Gnomad AMI

AF:

0.668

Gnomad AMR

AF:

0.854

Gnomad ASJ

AF:

0.835

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.782

Gnomad FIN

AF:

0.883

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.844

Gnomad OTH

AF:

0.847

GnomAD2 exomes

AF:

0.856

AC:

209568

AN:

244772

AF XY:

0.849

show subpopulations

Gnomad AFR exome

AF:

0.831

Gnomad AMR exome

AF:

0.885

Gnomad ASJ exome

AF:

0.834

Gnomad EAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.880

Gnomad NFE exome

AF:

0.847

Gnomad OTH exome

AF:

0.851

GnomAD4 exome

AF:

0.844

AC:

1231649

AN:

1459308

Hom.:

520871

Cov.:

AF XY:

0.842

AC XY:

610839

AN XY:

725830

show subpopulations

African (AFR)

AF:

0.836

AC:

27925

AN:

33392

American (AMR)

AF:

0.882

AC:

39268

AN:

44540

Ashkenazi Jewish (ASJ)

AF:

0.832

AC:

21650

AN:

26026

East Asian (EAS)

AF:

0.999

AC:

39640

AN:

39682

South Asian (SAS)

AF:

0.769

AC:

66037

AN:

85882

European-Finnish (FIN)

AF:

0.878

AC:

46769

AN:

53262

Middle Eastern (MID)

AF:

0.820

AC:

4722

AN:

5756

European-Non Finnish (NFE)

AF:

0.842

AC:

934745

AN:

1110506

Other (OTH)

AF:

0.845

AC:

50893

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.562

Heterozygous variant carriers

8372

16744

25117

33489

41861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21106

42212

63318

84424

105530

<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:

0.846

AC:

128497

AN:

151924

Hom.:

54474

Cov.:

AF XY:

0.847

AC XY:

62904

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.830

AC:

34399

AN:

41424

American (AMR)

AF:

0.854

AC:

13049

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.835

AC:

2896

AN:

3470

East Asian (EAS)

AF:

0.997

AC:

5105

AN:

5122

South Asian (SAS)

AF:

0.783

AC:

3769

AN:

4816

European-Finnish (FIN)

AF:

0.883

AC:

9326

AN:

10562

Middle Eastern (MID)

AF:

0.816

AC:

240

AN:

294

European-Non Finnish (NFE)

AF:

0.844

AC:

57314

AN:

67928

Other (OTH)

AF:

0.849

AC:

1790

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1011

2022

3033

4044

5055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.846

Hom.:

90195

Bravo

AF:

0.846

TwinsUK

AF:

0.831

AC:

3083

ALSPAC

AF:

0.838

AC:

3230

ESP6500AA

AF:

0.825

AC:

3636

ESP6500EA

AF:

0.839

AC:

7214

ExAC

AF:

0.851

AC:

103129

Asia WGS

AF:

0.919

AC:

3196

AN:

3478

EpiCase

AF:

0.839

EpiControl

AF:

0.845

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

MMP14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.048

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.12

MetaRNN

Benign

7.0e-7

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

-0.42

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.68

REVEL

Benign

0.062

Sift

Benign

1.0

Sift4G

Benign

0.93

Polyphen

0.0

Vest4

0.025

MPC

0.67

ClinPred

0.0051

GERP RS

2.5

PromoterAI

0.010

Neutral

(source)

Varity_R

0.028

gMVP

0.29

Mutation Taster

=91/9

polymorphism (auto)

(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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over