11-102843046-G-T

Variant names:

• chr11-102843046-G-T
• rs678815
• NM_002422.5:c.106-130C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002422.5(MMP3):​c.106-130C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 22 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5	c.106-130C>A		intron_variant	Intron 1 of 9	ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.106-130C>A		intron_variant	Intron 1 of 9	1	NM_002422.5	ENSP00000299855.5
MMP3	ENST00000524478.1	n.77-130C>A		intron_variant	Intron 1 of 3	4		ENSP00000435255.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 649682 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 328790

African (AFR) AF: 0.00 AC: 0 AN: 15536

American (AMR) AF: 0.00 AC: 0 AN: 16012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14366

East Asian (EAS) AF: 0.00 AC: 0 AN: 31042

South Asian (SAS) AF: 0.00 AC: 0 AN: 41086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2502

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 467958

Other (OTH) AF: 0.00 AC: 0 AN: 31866

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.024
DANN	Benign	0.14
PhyloP100		-1.5

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: rs678815; hg19: chr11-102713777;