chr11-102839352-G-A

Position:

• chr11-102839352-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002422.5(MMP3):​c.936-109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 1,277,590 control chromosomes in the GnomAD database, including 961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (134 hom., cov: 33)
  • Exomes 𝑓: 0.033 (827 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.212

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=-0.78).
• BP6: Variant 11-102839352-G-A is Benign according to our data. Variant chr11-102839352-G-A is described in ClinVar as [Benign]. Clinvar id is 1223368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0293 (4465/152226) while in subpopulation NFE AF= 0.0332 (2259/68004). AF 95% confidence interval is 0.0321. There are 134 homozygotes in gnomad4. There are 2462 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4465 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP3	NM_002422.5	c.936-109C>T		intron_variant		ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.936-109C>T		intron_variant		1	NM_002422.5	ENSP00000299855.5

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4470 AN: 152108 Hom.: 134 Cov.: 33

Gnomad AFR AF: 0.00592

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0328 AC: 36887 AN: 1125364 Hom.: 827 AF XY: 0.0318 AC XY: 18185 AN XY: 571946

Gnomad4 AFR exome AF: 0.00458

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.0379

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00653

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0333

Gnomad4 OTH exome AF: 0.0315

GnomAD4 genome AF: 0.0293 AC: 4465 AN: 152226 Hom.: 134 Cov.: 33 AF XY: 0.0331 AC XY: 2462 AN XY: 74420

Gnomad4 AFR AF: 0.00590

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00519

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0297 Hom.: 26

Bravo AF: 0.0214

Asia WGS AF: 0.00462 AC: 16 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	Jun 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.73

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: rs3025094; hg19: chr11-102710083;