rs17435959

Variant names:

Variant summary

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

The NM_002425.3(MMP10):c.10C>G(p.Leu4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 1,613,382 control chromosomes in the GnomAD database, including 2,113 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 0.071 ( 621 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1492 hom. )

Consequence

MMP10
NM_002425.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.14

Publications

26 publications found

Variant links:

Genes affected

MMP10 (HGNC:7156): (matrix metallopeptidase 10) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this 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. The encoded preproprotein is proteolytically processed to generate the mature protease. This secreted protease breaks down fibronectin, laminin, elastin, proteoglycan core protein, gelatins, and several types of collagen. The gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

MMP10 links:

WTAPP1 (HGNC:):

WTAPP1 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=0.0014594793).

BP6

Variant 11-102780582-G-C is Benign according to our data. Variant chr11-102780582-G-C is described in ClinVar as Benign. ClinVar VariationId is 1244144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP10	NM_002425.3 link	c.10C>G	p.Leu4Val	missense_variant	Exon 1 of 10	ENST00000279441.9	NP_002416.1	P09238

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP10	ENST00000279441.9 link	c.10C>G	p.Leu4Val	missense_variant	Exon 1 of 10	1	NM_002425.3	ENSP00000279441.4	P09238
MMP10	ENST00000539681.1 link	c.10C>G	p.Leu4Val	missense_variant	Exon 1 of 4	3		ENSP00000441485.1	F5GYX7
WTAPP1	ENST00000371455.7 link	n.325-17442G>C		intron_variant	Intron 2 of 4	4
WTAPP1	ENST00000817290.1 link	n.189-17442G>C		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.0712

AC:

10835

AN:

152116

Hom.:

618

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0423

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.0510

Gnomad SAS

AF:

0.0472

Gnomad FIN

AF:

0.0565

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0330

Gnomad OTH

AF:

0.0617

GnomAD2 exomes

AF:

0.0463

AC:

11592

AN:

250474

AF XY:

0.0447

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.0336

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.0563

Gnomad FIN exome

AF:

0.0568

Gnomad NFE exome

AF:

0.0315

Gnomad OTH exome

AF:

0.0393

GnomAD4 exome

AF:

0.0383

AC:

55970

AN:

1461148

Hom.:

1492

Cov.:

AF XY:

0.0383

AC XY:

27808

AN XY:

726836

show subpopulations

African (AFR)

AF:

0.166

AC:

5539

AN:

33440

American (AMR)

AF:

0.0361

AC:

1610

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.0223

AC:

583

AN:

26122

East Asian (EAS)

AF:

0.0533

AC:

2117

AN:

39686

South Asian (SAS)

AF:

0.0488

AC:

4207

AN:

86144

European-Finnish (FIN)

AF:

0.0558

AC:

2980

AN:

53384

Middle Eastern (MID)

AF:

0.0281

AC:

162

AN:

5764

European-Non Finnish (NFE)

AF:

0.0325

AC:

36114

AN:

1111622

Other (OTH)

AF:

0.0440

AC:

2658

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

2346

4691

7037

9382

11728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1480

2960

4440

5920

7400

<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:

0.0713

AC:

10855

AN:

152234

Hom.:

621

Cov.:

AF XY:

0.0711

AC XY:

5289

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.160

AC:

6628

AN:

41532

American (AMR)

AF:

0.0424

AC:

649

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3468

East Asian (EAS)

AF:

0.0511

AC:

265

AN:

5184

South Asian (SAS)

AF:

0.0468

AC:

226

AN:

4826

European-Finnish (FIN)

AF:

0.0565

AC:

599

AN:

10596

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0330

AC:

2245

AN:

68016

Other (OTH)

AF:

0.0606

AC:

128

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

493

987

1480

1974

2467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0378

Hom.:

119

Bravo

AF:

0.0748

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0317

AC:

122

ESP6500AA

AF:

0.154

AC:

678

ESP6500EA

AF:

0.0305

AC:

262

ExAC

AF:

0.0483

AC:

5864

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

EpiCase

AF:

0.0309

EpiControl

AF:

0.0301

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 24, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26419737) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.5

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.41

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

M;.

PhyloP100

1.1

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.059

Sift

Benign

0.045

D;T

Sift4G

Uncertain

0.055

T;.

Polyphen

0.91

P;.

Vest4

0.074

MPC

0.032

ClinPred

0.026

GERP RS

1.6

PromoterAI

0.0039

Neutral

(source)

Varity_R

0.052

gMVP

0.41

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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