Variant 12-131851047-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP17	NM_016155.7 linkuse as main transcript	c.1585G>A	p.Asp529Asn	missense_variant	10/10	ENST00000360564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP17	ENST00000360564.5 linkuse as main transcript	c.1585G>A	p.Asp529Asn	missense_variant	10/10	1	NM_016155.7	P1	Q9ULZ9-1

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

GnomAD3 exomes

AF:

0.183

AC:

43923

AN:

240422

Hom.:

4440

AF XY:

0.184

AC XY:

24086

AN XY:

131088

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 SAS exome

AF:

0.142

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

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.000686

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.201

GnomAD4 genome

AF:

0.196

AC:

29863

AN:

152210

Hom.:

3085

Cov.:

AF XY:

0.195

AC XY:

14532

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.194

Hom.:

3767

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;.;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.61

T;T;T

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.97

L;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.073

Sift

Benign

0.045

D;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.040

B;.;.

Vest4

0.094

MPC

0.20

ClinPred

0.0088

GERP RS

1.5

Varity_R

0.094

gMVP

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over