rs1042704

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.817G>A(p.Asp273Asn) variant causes a missense change. The variant allele was found at a frequency of 0.191 in 1,613,702 control chromosomes in the GnomAD database, including 31,921 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 0.14 ( 2021 hom., cov: 31)

Exomes 𝑓: 0.20 ( 29900 hom. )

Consequence

MMP14
NM_004995.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.88

Publications

65 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=0.0025402606).

BP6

Variant 14-22843385-G-A is Benign according to our data. Variant chr14-22843385-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP14	NM_004995.4 link	c.817G>A	p.Asp273Asn	missense_variant	Exon 5 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.817G>A	p.Asp273Asn	missense_variant	Exon 5 of 10	1	NM_004995.4	ENSP00000308208.6		P50281

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21779

AN:

151996

Hom.:

2020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0390

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0236

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.135

GnomAD2 exomes

AF:

0.164

AC:

41229

AN:

251266

AF XY:

0.171

show subpopulations

Gnomad AFR exome

AF:

0.0356

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.0184

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.196

AC:

286595

AN:

1461588

Hom.:

29900

Cov.:

AF XY:

0.198

AC XY:

143655

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.0310

AC:

1037

AN:

33480

American (AMR)

AF:

0.105

AC:

4680

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

3743

AN:

26130

East Asian (EAS)

AF:

0.0163

AC:

649

AN:

39700

South Asian (SAS)

AF:

0.222

AC:

19166

AN:

86248

European-Finnish (FIN)

AF:

0.208

AC:

11097

AN:

53254

Middle Eastern (MID)

AF:

0.142

AC:

818

AN:

5768

European-Non Finnish (NFE)

AF:

0.211

AC:

234722

AN:

1111902

Other (OTH)

AF:

0.177

AC:

10683

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

12272

24544

36816

49088

61360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8050

16100

24150

32200

40250

<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:

0.143

AC:

21780

AN:

152114

Hom.:

2021

Cov.:

AF XY:

0.142

AC XY:

10567

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0389

AC:

1616

AN:

41520

American (AMR)

AF:

0.117

AC:

1782

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

533

AN:

3472

East Asian (EAS)

AF:

0.0230

AC:

119

AN:

5164

South Asian (SAS)

AF:

0.216

AC:

1041

AN:

4812

European-Finnish (FIN)

AF:

0.205

AC:

2164

AN:

10572

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14041

AN:

67974

Other (OTH)

AF:

0.137

AC:

289

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

916

1832

2747

3663

4579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.180

Hom.:

10636

Bravo

AF:

0.128

TwinsUK

AF:

0.215

AC:

797

ALSPAC

AF:

0.221

AC:

852

ESP6500AA

AF:

0.0447

AC:

197

ESP6500EA

AF:

0.203

AC:

1747

ExAC

AF:

0.164

AC:

19845

Asia WGS

AF:

0.139

AC:

484

AN:

3478

EpiCase

AF:

0.198

EpiControl

AF:

0.198

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.081

Eigen

Benign

-0.13

Eigen_PC

Benign

0.035

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

4.9

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

REVEL

Benign

0.085

Sift

Benign

0.41

Sift4G

Benign

0.35

Polyphen

0.0050

Vest4

0.10

MPC

0.31

ClinPred

0.0076

GERP RS

5.6

Varity_R

0.39

gMVP

0.49

Mutation Taster

=79/21

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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