chr11-102839352-G-A

Variant names:

• chr11-102839352-G-A
• rs3025094
• NM_002422.5:c.936-109C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4465 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002422.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP3	NM_002422.5	MANE Select	c.936-109C>T		intron	N/A	NP_002413.1	P08254

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP3	ENST00000299855.10	TSL:1 MANE Select	c.936-109C>T		intron	N/A	ENSP00000299855.5	P08254

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

African (AFR) AF: 0.00458 AC: 113 AN: 24658

American (AMR) AF: 0.0181 AC: 564 AN: 31156

Ashkenazi Jewish (ASJ) AF: 0.0379 AC: 873 AN: 23038

East Asian (EAS) AF: 0.00 AC: 0 AN: 36542

South Asian (SAS) AF: 0.00653 AC: 470 AN: 71934

European-Finnish (FIN) AF: 0.108 AC: 5435 AN: 50388

Middle Eastern (MID) AF: 0.0332 AC: 128 AN: 3858

European-Non Finnish (NFE) AF: 0.0333 AC: 27767 AN: 835062

Other (OTH) AF: 0.0315 AC: 1537 AN: 48728

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

African (AFR) AF: 0.00590 AC: 245 AN: 41542

American (AMR) AF: 0.0221 AC: 338 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00519 AC: 25 AN: 4820

European-Finnish (FIN) AF: 0.130 AC: 1380 AN: 10584

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0332 AC: 2259 AN: 68004

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0306 Hom.: 36

Bravo AF: 0.0214

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.73
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism

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: rs3025094; hg19: chr11-102710083;