rs646910

Positions:

• chr11-102838791-T-A

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.1070-81A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,440,300 control chromosomes in the GnomAD database, including 12,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1259 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11057 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.145

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=-0.74).
• BP6: Variant 11-102838791-T-A is Benign according to our data. Variant chr11-102838791-T-A is described in ClinVar as [Benign]. Clinvar id is 1274196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP3	NM_002422.5	c.1070-81A>T		intron_variant		ENST00000299855.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP3	ENST00000299855.10	c.1070-81A>T		intron_variant		1	NM_002422.5	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16432 AN: 152118 Hom.: 1259 Cov.: 33

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.124 AC: 160357 AN: 1288064 Hom.: 11057 AF XY: 0.124 AC XY: 79256 AN XY: 640600

Gnomad4 AFR exome AF: 0.0285

Gnomad4 AMR exome AF: 0.0771

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.0982

Gnomad4 SAS exome AF: 0.0824

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.108 AC: 16433 AN: 152236 Hom.: 1259 Cov.: 33 AF XY: 0.112 AC XY: 8335 AN XY: 74420

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.0858

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0723

Gnomad4 SAS AF: 0.0791

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.107

Alfa AF: 0.126 Hom.: 184

Bravo AF: 0.0911

Asia WGS AF: 0.0690 AC: 239 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	-0.74
CADD	Benign	10
DANN	Benign	0.82

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: rs646910; hg19: chr11-102709522;