11-102838056-G-A

Variant names:

• chr11-102838056-G-A
• rs650108
• NM_002422.5:c.1229+495C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 61 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 -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.

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.1229+495C>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.1229+495C>T		intron	N/A	ENSP00000299855.5	P08254
	MMP3	ENST00000434103.1	TSL:3	c.158+495C>T		intron	N/A	ENSP00000398346.1	H7C139

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

African (AFR) AF: 0.308 AC: 12757 AN: 41436

American (AMR) AF: 0.458 AC: 6998 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1229 AN: 3472

East Asian (EAS) AF: 0.601 AC: 3106 AN: 5168

South Asian (SAS) AF: 0.550 AC: 2653 AN: 4824

European-Finnish (FIN) AF: 0.273 AC: 2866 AN: 10492

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17810 AN: 67974

Other (OTH) AF: 0.324 AC: 683 AN: 2110

Alfa AF: 0.275 Hom.: 2508

Bravo AF: 0.331

Asia WGS AF: 0.528 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.67
DANN	Benign	0.63
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs650108; hg19: chr11-102708787;