rs678815

Variant names:

• chr11-102843046-G-A
• rs678815
• NM_002422.5:c.106-130C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-102843046-G-A
• chr11-102843046-G-C
• chr11-102843046-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002422.5(MMP3):​c.106-130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 801,232 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 22 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.106-130C>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.106-130C>T		intron	N/A	ENSP00000299855.5	P08254
	MMP3	ENST00000524478.1	TSL:4	n.77-130C>T		intron	N/A	ENSP00000435255.1	E9PKX2

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151554 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 4 AN: 649678 Hom.: 0 AF XY: 0.00000608 AC XY: 2 AN XY: 328788

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15536

American (AMR) AF: 0.00 AC: 0 AN: 16012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14366

East Asian (EAS) AF: 0.00 AC: 0 AN: 31042

South Asian (SAS) AF: 0.0000730 AC: 3 AN: 41084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2502

European-Non Finnish (NFE) AF: 0.00000214 AC: 1 AN: 467956

Other (OTH) AF: 0.00 AC: 0 AN: 31866

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151554 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73946

African (AFR) AF: 0.00 AC: 0 AN: 41204

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67908

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 1162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.029
DANN	Benign	0.91
PhyloP100		-1.5

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: rs678815; hg19: chr11-102713777;