rs566125

Variant names:

• chr11-102839740-C-T
• rs566125
• NM_002422.5:c.935+368G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002422.5(MMP3):​c.935+368G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,142 control chromosomes in the GnomAD database, including 1,239 homozygotes. 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: 𝑓 0.10 (1239 hom., cov: 33)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990
• Publications: 20 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5	c.935+368G>A		intron_variant	Intron 6 of 9	ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.935+368G>A		intron_variant	Intron 6 of 9	1	NM_002422.5	ENSP00000299855.5

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15932 AN: 152024 Hom.: 1239 Cov.: 33

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 15932 AN: 152142 Hom.: 1239 Cov.: 33 AF XY: 0.109 AC XY: 8101 AN XY: 74354

African (AFR) AF: 0.0248 AC: 1028 AN: 41526

American (AMR) AF: 0.0840 AC: 1284 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3468

East Asian (EAS) AF: 0.0724 AC: 375 AN: 5182

South Asian (SAS) AF: 0.0796 AC: 383 AN: 4814

European-Finnish (FIN) AF: 0.279 AC: 2945 AN: 10550

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9121 AN: 67996

Other (OTH) AF: 0.103 AC: 218 AN: 2112

Alfa AF: 0.122 Hom.: 3249

Bravo AF: 0.0876

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.74
DANN	Benign	0.61
PhyloP100		-0.99
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: rs566125; hg19: chr11-102710471;