Genetic Variant MMP3:c.*153G>A (chr11-102835973-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_002422.5(MMP3):c.*153G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00674 in 604,456 control chromosomes in the GnomAD database, including 127 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 0.019 ( 90 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 37 hom. )

Consequence

MMP3
NM_002422.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.873

Publications

4 publications found

Variant links:

Genes affected

MMP3 (HGNC:7173): (matrix metallopeptidase 3) Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. [provided by RefSeq, Jul 2008]

MMP3 links:

WTAPP1 (HGNC:):

WTAPP1 links:

WTAPP1 (HGNC:44115): (WTAP pseudogene 1)

WTAPP1 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5 link	c.*153G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000299855.10	NP_002413.1
WTAPP1	NR_038390.1 link	n.2314-465C>T		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10 link	c.*153G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_002422.5	ENSP00000299855.5
WTAPP1	ENST00000525739.6 link	n.2314-465C>T		intron_variant	Intron 7 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2856

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00909

GnomAD4 exome

AF:

0.00267

AC:

1209

AN:

452282

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

529

AN XY:

237284

show subpopulations

African (AFR)

AF:

0.0709

AC:

894

AN:

12602

American (AMR)

AF:

0.00366

AC:

AN:

18874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13236

East Asian (EAS)

AF:

0.00

AC:

AN:

31130

South Asian (SAS)

AF:

0.000326

AC:

AN:

39904

European-Finnish (FIN)

AF:

0.0000976

AC:

AN:

40968

Middle Eastern (MID)

AF:

0.00296

AC:

AN:

2704

European-Non Finnish (NFE)

AF:

0.000284

AC:

AN:

267392

Other (OTH)

AF:

0.00569

AC:

145

AN:

25472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0188

AC:

2866

AN:

152174

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1366

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0655

AC:

2719

AN:

41518

American (AMR)

AF:

0.00615

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000471

AC:

AN:

68008

Other (OTH)

AF:

0.00900

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

134

267

401

534

668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00861

Hom.:

Bravo

AF:

0.0216

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.18

(source)

DANN

Benign

0.73

PhyloP100

-0.87

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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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