11-102842734-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002422.5(MMP3):​c.288T>C​(p.Asp96Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,613,446 control chromosomes in the GnomAD database, including 222,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (22942 hom., cov: 31)
  • Exomes 𝑓: 0.52 (199729 hom.)
• Consequence: MMP3 NM_002422.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-102842734-A-G is Benign according to our data. Variant chr11-102842734-A-G is described in ClinVar as Benign. ClinVar VariationId is 403097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.36 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

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>C	p.Asp96Asp	synonymous	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>C	p.Asp96Asp	synonymous	Exon 2 of 10	ENSP00000299855.5	P08254
	MMP3	ENST00000524478.1	TSL:4	n.*130T>C		non_coding_transcript_exon	Exon 2 of 4	ENSP00000435255.1	E9PKX2
	MMP3	ENST00000524478.1	TSL:4	n.*130T>C		3_prime_UTR	Exon 2 of 4	ENSP00000435255.1	E9PKX2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82732 AN: 151746 Hom.: 22910 Cov.: 31

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.573 AC: 143688 AN: 250880 AF XY: 0.571

Gnomad AFR exome AF: 0.546

Gnomad AMR exome AF: 0.699

Gnomad ASJ exome AF: 0.606

Gnomad EAS exome AF: 0.666

Gnomad FIN exome AF: 0.589

Gnomad NFE exome AF: 0.491

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.518 AC: 757194 AN: 1461582 Hom.: 199729 Cov.: 64 AF XY: 0.523 AC XY: 380508 AN XY: 727052

African (AFR) AF: 0.548 AC: 18337 AN: 33468

American (AMR) AF: 0.690 AC: 30825 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 15918 AN: 26132

East Asian (EAS) AF: 0.679 AC: 26957 AN: 39692

South Asian (SAS) AF: 0.674 AC: 58105 AN: 86254

European-Finnish (FIN) AF: 0.584 AC: 31203 AN: 53396

Middle Eastern (MID) AF: 0.610 AC: 3515 AN: 5766

European-Non Finnish (NFE) AF: 0.486 AC: 539927 AN: 1111838

Other (OTH) AF: 0.537 AC: 32407 AN: 60374

GnomAD4 genome AF: 0.545 AC: 82815 AN: 151864 Hom.: 22942 Cov.: 31 AF XY: 0.555 AC XY: 41148 AN XY: 74194

African (AFR) AF: 0.548 AC: 22704 AN: 41406

American (AMR) AF: 0.628 AC: 9579 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2133 AN: 3468

East Asian (EAS) AF: 0.674 AC: 3464 AN: 5142

South Asian (SAS) AF: 0.697 AC: 3352 AN: 4812

European-Finnish (FIN) AF: 0.606 AC: 6383 AN: 10530

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33373 AN: 67950

Other (OTH) AF: 0.539 AC: 1129 AN: 2094

Alfa AF: 0.484 Hom.: 7114

Bravo AF: 0.546

Asia WGS AF: 0.660 AC: 2294 AN: 3478

EpiCase AF: 0.499

EpiControl AF: 0.500

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.036
DANN	Benign	0.28
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs602128; hg19: chr11-102713465; COSMIC: COSV55406163; COSMIC: COSV55406163;