Variant rs3743563 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002428.4(MMP15):c.1825G>A(p.Gly609Arg) variant causes a missense change. The variant allele was found at a frequency of 0.217 in 1,608,266 control chromosomes in the GnomAD database, including 41,416 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3364 hom., cov: 33)

Exomes 𝑓: 0.22 ( 38052 hom. )

Consequence

MMP15
NM_002428.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.84

Variant links:

Genes affected

MMP15 (HGNC:7161): (matrix metallopeptidase 15) 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 may play a role in cancer progression. [provided by RefSeq, Jan 2016]

MMP15 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=0.0037374198).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP15	NM_002428.4 linkuse as main transcript	c.1825G>A	p.Gly609Arg	missense_variant	10/10	ENST00000219271.4	NP_002419.1	P51511A0A024R6U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP15	ENST00000219271.4 linkuse as main transcript	c.1825G>A	p.Gly609Arg	missense_variant	10/10	1	NM_002428.4	ENSP00000219271.3		P51511

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28400

AN:

152108

Hom.:

3355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0649

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.170

GnomAD3 exomes

AF:

0.237

AC:

56369

AN:

237644

Hom.:

8129

AF XY:

0.227

AC XY:

29208

AN XY:

128610

show subpopulations

Gnomad AFR exome

AF:

0.0614

Gnomad AMR exome

AF:

0.441

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.341

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.220

AC:

319777

AN:

1456040

Hom.:

38052

Cov.:

AF XY:

0.216

AC XY:

156602

AN XY:

723798

show subpopulations

Gnomad4 AFR exome

AF:

0.0537

Gnomad4 AMR exome

AF:

0.425

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.348

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.215

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.187

AC:

28421

AN:

152226

Hom.:

3364

Cov.:

AF XY:

0.194

AC XY:

14435

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0648

Gnomad4 AMR

AF:

0.304

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.342

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.312

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.192

Hom.:

1290

Bravo

AF:

0.185

TwinsUK

AF:

0.203

AC:

751

ALSPAC

AF:

0.213

AC:

821

ESP6500AA

AF:

0.0701

AC:

308

ESP6500EA

AF:

0.191

AC:

1645

ExAC

AF:

0.216

AC:

26065

Asia WGS

AF:

0.254

AC:

884

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.1

REVEL

Benign

0.038

Sift

Benign

0.075

Sift4G

Benign

0.50

Polyphen

0.092

Vest4

0.081

MutPred

0.11

Gain of MoRF binding (P = 0.032);

MPC

0.65

ClinPred

0.021

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.1

Varity_R

0.091

gMVP

0.37

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