11-102843046-G-C

Position:

• chr11-102843046-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002422.5(MMP3):​c.106-130C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 798,894 control chromosomes in the GnomAD database, including 111,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25092 hom., cov: 30)
  • Exomes 𝑓: 0.51 (86736 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.48

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-102843046-G-C is Benign according to our data. Variant chr11-102843046-G-C is described in ClinVar as [Benign]. Clinvar id is 1262266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
MMP3	NM_002422.5	c.106-130C>G		intron_variant		ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.106-130C>G		intron_variant		1	NM_002422.5	ENSP00000299855.5
MMP3	ENST00000524478.1	n.77-130C>G		intron_variant		4		ENSP00000435255.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86293 AN: 151444 Hom.: 25054 Cov.: 30

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.509 AC: 329405 AN: 647334 Hom.: 86736 AF XY: 0.515 AC XY: 168825 AN XY: 327622

Gnomad4 AFR exome AF: 0.635

Gnomad4 AMR exome AF: 0.663

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.681

Gnomad4 SAS exome AF: 0.670

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.535

GnomAD4 genome AF: 0.570 AC: 86385 AN: 151560 Hom.: 25092 Cov.: 30 AF XY: 0.579 AC XY: 42852 AN XY: 74018

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.555

Alfa AF: 0.397 Hom.: 1162

Bravo AF: 0.574

Asia WGS AF: 0.666 AC: 2314 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.024
DANN	Benign	0.59

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: rs678815; hg19: chr11-102713777;