11-102837183-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002422.5(MMP3):c.1333+115T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 706,526 control chromosomes in the GnomAD database, including 105,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (23049 hom., cov: 32)
  • Exomes 𝑓: 0.54 (82122 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.713

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-102837183-A-G is Benign according to our data. Variant chr11-102837183-A-G is described in ClinVar as [Benign]. Clinvar id is 1286978.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP3	NM_002422.5	c.1333+115T>C		intron_variant		ENST00000299855.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP3	ENST00000299855.10	c.1333+115T>C		intron_variant		1	NM_002422.5	P1
MMP3	ENST00000434103.1	c.264+115T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82940 AN: 151890 Hom.: 23016 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.538

GnomAD4 exome AF: 0.537 AC: 297934 AN: 554518 Hom.: 82122 AF XY: 0.543 AC XY: 158237 AN XY: 291320

Gnomad4 AFR exome AF: 0.554

Gnomad4 AMR exome AF: 0.670

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.678

Gnomad4 FIN exome AF: 0.589

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.542

GnomAD4 genome AF: 0.546 AC: 83024 AN: 152008 Hom.: 23049 Cov.: 32 AF XY: 0.555 AC XY: 41269 AN XY: 74292

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.539

Alfa AF: 0.510 Hom.: 4497

Bravo AF: 0.547

Asia WGS AF: 0.663 AC: 2304 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.27
Dann	Benign	0.51

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

Other links and lift over

dbSNP: rs575027; hg19: chr11-102707914; COSMIC: COSV55405926; COSMIC: COSV55405926;