Genetic Variant MMP15:c.163-113C>T (chr16-58037359-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002428.4(MMP15):c.163-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,374,472 control chromosomes in the GnomAD database, including 2,209 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.049 ( 181 hom., cov: 33)

Exomes 𝑓: 0.054 ( 2028 hom. )

Consequence

MMP15
NM_002428.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.98

Publications

2 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP15	NM_002428.4 link	c.163-113C>T		intron_variant	Intron 1 of 9	ENST00000219271.4	NP_002419.1	P51511A0A024R6U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP15	ENST00000219271.4 link	c.163-113C>T		intron_variant	Intron 1 of 9	1	NM_002428.4	ENSP00000219271.3		P51511

Frequencies

GnomAD3 genomes

AF:

0.0487

AC:

7408

AN:

152110

Hom.:

180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0466

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0462

Gnomad ASJ

AF:

0.0665

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0419

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0603

GnomAD4 exome

AF:

0.0542

AC:

66249

AN:

1222244

Hom.:

2028

AF XY:

0.0542

AC XY:

32925

AN XY:

607402

show subpopulations

African (AFR)

AF:

0.0496

AC:

1408

AN:

28404

American (AMR)

AF:

0.0339

AC:

1216

AN:

35866

Ashkenazi Jewish (ASJ)

AF:

0.0719

AC:

1453

AN:

20206

East Asian (EAS)

AF:

0.000236

AC:

AN:

38212

South Asian (SAS)

AF:

0.0441

AC:

3096

AN:

70156

European-Finnish (FIN)

AF:

0.0287

AC:

1309

AN:

45548

Middle Eastern (MID)

AF:

0.0939

AC:

406

AN:

4324

European-Non Finnish (NFE)

AF:

0.0587

AC:

54473

AN:

927822

Other (OTH)

AF:

0.0557

AC:

2879

AN:

51706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

3042

6084

9127

12169

15211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0487

AC:

7415

AN:

152228

Hom.:

181

Cov.:

AF XY:

0.0471

AC XY:

3509

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0467

AC:

1939

AN:

41538

American (AMR)

AF:

0.0462

AC:

706

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0665

AC:

231

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0418

AC:

201

AN:

4814

European-Finnish (FIN)

AF:

0.0303

AC:

321

AN:

10602

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0568

AC:

3866

AN:

68004

Other (OTH)

AF:

0.0601

AC:

127

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

371

741

1112

1482

1853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0502

Hom.:

Bravo

AF:

0.0499

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.40

(source)

DANN

Benign

0.49

PhyloP100

-3.0

Mutation Taster

=100/0

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

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16-58037359-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over