14-22843714-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004995.4(MMP14):c.855T>C(p.Gly285Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,585,932 control chromosomes in the GnomAD database, including 38,274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4628 hom., cov: 31)

Exomes 𝑓: 0.21 ( 33646 hom. )

Consequence

MMP14
NM_004995.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.841

Publications

26 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-22843714-T-C is Benign according to our data. Variant chr14-22843714-T-C is described in ClinVar as Benign. ClinVar VariationId is 1177852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.841 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP14	NM_004995.4 link	c.855T>C	p.Gly285Gly	synonymous_variant	Exon 6 of 10	ENST00000311852.11	NP_004986.1	P50281

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP14	ENST00000311852.11 link	c.855T>C	p.Gly285Gly	synonymous_variant	Exon 6 of 10	1	NM_004995.4	ENSP00000308208.6		P50281

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

35999

AN:

151342

Hom.:

4609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.376

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.252

GnomAD2 exomes

AF:

0.217

AC:

48562

AN:

224188

AF XY:

0.216

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.375

Gnomad FIN exome

AF:

0.163

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.212

AC:

304378

AN:

1434474

Hom.:

33646

Cov.:

AF XY:

0.212

AC XY:

151448

AN XY:

713424

show subpopulations

African (AFR)

AF:

0.316

AC:

9921

AN:

31354

American (AMR)

AF:

0.137

AC:

4850

AN:

35324

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

4868

AN:

24756

East Asian (EAS)

AF:

0.385

AC:

15149

AN:

39364

South Asian (SAS)

AF:

0.224

AC:

18414

AN:

82056

European-Finnish (FIN)

AF:

0.163

AC:

8667

AN:

53168

Middle Eastern (MID)

AF:

0.249

AC:

1405

AN:

5642

European-Non Finnish (NFE)

AF:

0.206

AC:

227886

AN:

1103632

Other (OTH)

AF:

0.223

AC:

13218

AN:

59178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

12274

24548

36823

49097

61371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8064

16128

24192

32256

40320

<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:

0.238

AC:

36058

AN:

151458

Hom.:

4628

Cov.:

AF XY:

0.236

AC XY:

17496

AN XY:

74010

show subpopulations

African (AFR)

AF:

0.310

AC:

12776

AN:

41208

American (AMR)

AF:

0.203

AC:

3093

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

676

AN:

3470

East Asian (EAS)

AF:

0.376

AC:

1919

AN:

5098

South Asian (SAS)

AF:

0.231

AC:

1102

AN:

4778

European-Finnish (FIN)

AF:

0.161

AC:

1693

AN:

10530

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

13972

AN:

67864

Other (OTH)

AF:

0.257

AC:

539

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1298

2597

3895

5194

6492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.216

Hom.:

4206

Bravo

AF:

0.245

Asia WGS

AF:

0.331

AC:

1150

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

MMP14-related disorder

Benign:1

Nov 12, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.3

(source)

DANN

Benign

0.60

PhyloP100

0.84

Mutation Taster

=100/0

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

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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