rs602128

Variant names:

• chr11-102842734-A-C
• rs602128
• NM_002422.5:c.288T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-102842734-A-C
• chr11-102842734-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002422.5(MMP3):​c.288T>G​(p.Asp96Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. D96D) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MMP3 NM_002422.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 52 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002422.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP3	NM_002422.5	MANE Select	c.288T>G	p.Asp96Glu	missense	Exon 2 of 10	NP_002413.1	P08254

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP3	ENST00000299855.10	TSL:1 MANE Select	c.288T>G	p.Asp96Glu	missense	Exon 2 of 10	ENSP00000299855.5	P08254
	MMP3	ENST00000524478.1	TSL:4	n.*130T>G		non_coding_transcript_exon	Exon 2 of 4	ENSP00000435255.1	E9PKX2
	MMP3	ENST00000524478.1	TSL:4	n.*130T>G		3_prime_UTR	Exon 2 of 4	ENSP00000435255.1	E9PKX2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151832 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250880 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461616 Hom.: 0 Cov.: 64 AF XY: 0.00000413 AC XY: 3 AN XY: 727072

African (AFR) AF: 0.0000598 AC: 2 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151832 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74120

African (AFR) AF: 0.0000484 AC: 2 AN: 41302

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 7114

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	0.066
DANN	Benign	0.97
DEOGEN2	Uncertain	0.68	D
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.077	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.65	D
MutationAssessor	Pathogenic	4.4	H
PhyloP100		-2.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.64		Gain of methylation at R101 (P = 0.1445)
MVP		0.77
MPC		0.13
ClinPred		0.99	D
GERP RS		-12
Varity_R		0.77
gMVP		0.88
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs602128; hg19: chr11-102713465;