11-102838056-G-A

Position:

• chr11-102838056-G-A

Variant summary

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

The NM_002422.5(MMP3):​c.1229+495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,954 control chromosomes in the GnomAD database, including 8,486 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 0.32 (8486 hom., cov: 32)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP3	NM_002422.5	c.1229+495C>T		intron_variant		ENST00000299855.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP3	ENST00000299855.10	c.1229+495C>T		intron_variant		1	NM_002422.5	P1
MMP3	ENST00000434103.1	c.160+495C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48419 AN: 151836 Hom.: 8458 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.319 AC: 48477 AN: 151954 Hom.: 8486 Cov.: 32 AF XY: 0.327 AC XY: 24281 AN XY: 74244

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.324

Alfa AF: 0.190 Hom.: 461

Bravo AF: 0.331

Asia WGS AF: 0.528 AC: 1836 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	0.67
DANN	Benign	0.63

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: rs650108; hg19: chr11-102708787;