rs3025066

Positions:

• chr11-102839752-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002422.5(MMP3):​c.935+356A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 152,332 control chromosomes in the GnomAD database, including 230 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 0.048 (230 hom., cov: 33)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP3	NM_002422.5	c.935+356A>G		intron_variant		ENST00000299855.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP3	ENST00000299855.10	c.935+356A>G		intron_variant		1	NM_002422.5	P1

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7258 AN: 152214 Hom.: 230 Cov.: 33

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0476 AC: 7255 AN: 152332 Hom.: 230 Cov.: 33 AF XY: 0.0464 AC XY: 3457 AN XY: 74488

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0514

Gnomad4 ASJ AF: 0.0534

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00851

Gnomad4 FIN AF: 0.0686

Gnomad4 NFE AF: 0.0707

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0660 Hom.: 379

Bravo AF: 0.0446

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.75

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: rs3025066; hg19: chr11-102710483;