Genetic Variant NM_016155.7:c.1585G>A (chr12-131851047-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016155.7(MMP17):c.1585G>A(p.Asp529Asn) variant causes a missense change. The variant allele was found at a frequency of 0.206 in 1,607,916 control chromosomes in the GnomAD database, including 35,848 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3085 hom., cov: 33)

Exomes 𝑓: 0.21 ( 32763 hom. )

Consequence

MMP17
NM_016155.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65

Publications

20 publications found

Variant links:

Genes affected

MMP17 (HGNC:7163): (matrix metallopeptidase 17) This gene encodes a member of the peptidase M10 family and membrane-type subfamily 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. Members of this subfamily contain a transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. The encoded preproprotein is proteolytically processed to generate the mature protease. This protein is unique among the membrane-type matrix metalloproteinases in that it is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. Elevated expression of the encoded protein has been observed in osteoarthritis and multiple human cancers. [provided by RefSeq, Jan 2016]

MMP17 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043974817).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016155.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP17	NM_016155.7	MANE Select	c.1585G>A	p.Asp529Asn	missense	Exon 10 of 10	NP_057239.4
MMP17	NM_001411000.1		c.1333G>A	p.Asp445Asn	missense	Exon 10 of 10	NP_001397929.1	Q9ULZ9-2
MMP17	NR_182296.1		n.1869G>A		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP17	ENST00000360564.5	TSL:1 MANE Select	c.1585G>A	p.Asp529Asn	missense	Exon 10 of 10	ENSP00000353767.1	Q9ULZ9-1
MMP17	ENST00000535291.5	TSL:1	c.1333G>A	p.Asp445Asn	missense	Exon 9 of 9	ENSP00000441106.1	Q9ULZ9-2
MMP17	ENST00000912510.1		c.1603G>A	p.Asp535Asn	missense	Exon 11 of 11	ENSP00000582569.1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29829

AN:

152092

Hom.:

3078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.208

GnomAD2 exomes

AF:

0.183

AC:

43923

AN:

240422

AF XY:

0.184

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.000950

Gnomad FIN exome

AF:

0.241

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.207

AC:

301704

AN:

1455706

Hom.:

32763

Cov.:

AF XY:

0.205

AC XY:

148781

AN XY:

724026

show subpopulations

African (AFR)

AF:

0.177

AC:

5906

AN:

33280

American (AMR)

AF:

0.168

AC:

7407

AN:

44118

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

5084

AN:

25896

East Asian (EAS)

AF:

0.000686

AC:

AN:

39380

South Asian (SAS)

AF:

0.142

AC:

12185

AN:

85614

European-Finnish (FIN)

AF:

0.239

AC:

12431

AN:

52058

Middle Eastern (MID)

AF:

0.175

AC:

1002

AN:

5742

European-Non Finnish (NFE)

AF:

0.221

AC:

245581

AN:

1109550

Other (OTH)

AF:

0.201

AC:

12081

AN:

60068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

13281

26563

39844

53126

66407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8376

16752

25128

33504

41880

<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:

0.196

AC:

29863

AN:

152210

Hom.:

3085

Cov.:

AF XY:

0.195

AC XY:

14532

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.182

AC:

7565

AN:

41542

American (AMR)

AF:

0.199

AC:

3046

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

649

AN:

3468

East Asian (EAS)

AF:

0.00135

AC:

AN:

5186

South Asian (SAS)

AF:

0.127

AC:

611

AN:

4830

European-Finnish (FIN)

AF:

0.232

AC:

2462

AN:

10596

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14873

AN:

67982

Other (OTH)

AF:

0.209

AC:

441

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1247

2493

3740

4986

6233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.197

Hom.:

5610

Bravo

AF:

0.191

TwinsUK

AF:

0.226

AC:

838

ALSPAC

AF:

0.212

AC:

818

ESP6500AA

AF:

0.180

AC:

791

ESP6500EA

AF:

0.216

AC:

1858

ExAC

AF:

0.182

AC:

21978

Asia WGS

AF:

0.0790

AC:

277

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.97

PhyloP100

3.6

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.4

REVEL

Benign

0.073

Sift

Benign

0.045

Sift4G

Benign

0.11

Polyphen

0.040

Vest4

0.094

MPC

0.20

ClinPred

0.0088

GERP RS

1.5

Varity_R

0.094

gMVP

0.65

Mutation Taster

=95/5

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

Computational scores

Splicing

Publications

Other links and lift over