rs679620

Variant names:

• chr11-102842889-T-C
• rs679620
• NM_002422.5:c.133A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-102842889-T-C
• chr11-102842889-T-A
• chr11-102842889-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002422.5(MMP3):​c.133A>G​(p.Lys45Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,608,044 control chromosomes in the GnomAD database, including 227,326 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (25701 hom., cov: 31)
  • Exomes 𝑓: 0.52 (201625 hom.)
• Consequence: MMP3 NM_002422.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.176
• Publications: 196 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 (MetaRNN=1.954977E-6).
• BP6: Variant 11-102842889-T-C is Benign according to our data. Variant chr11-102842889-T-C is described in ClinVar as Benign. ClinVar VariationId is 403098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 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.133A>G	p.Lys45Glu	missense	Exon 2 of 10	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.133A>G	p.Lys45Glu	missense	Exon 2 of 10	ENSP00000299855.5	P08254
	MMP3	ENST00000524478.1	TSL:4	n.104A>G		non_coding_transcript_exon	Exon 2 of 4	ENSP00000435255.1	E9PKX2

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87307 AN: 151766 Hom.: 25663 Cov.: 31

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.559

GnomAD2 exomes AF: 0.580 AC: 142818 AN: 246160 AF XY: 0.576

Gnomad AFR exome AF: 0.653

Gnomad AMR exome AF: 0.703

Gnomad ASJ exome AF: 0.606

Gnomad EAS exome AF: 0.666

Gnomad FIN exome AF: 0.589

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.521 AC: 758719 AN: 1456160 Hom.: 201625 Cov.: 37 AF XY: 0.526 AC XY: 380836 AN XY: 724274

African (AFR) AF: 0.659 AC: 21951 AN: 33328

American (AMR) AF: 0.695 AC: 30762 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 15862 AN: 26038

East Asian (EAS) AF: 0.679 AC: 26897 AN: 39620

South Asian (SAS) AF: 0.674 AC: 57923 AN: 85936

European-Finnish (FIN) AF: 0.584 AC: 31084 AN: 53198

Middle Eastern (MID) AF: 0.615 AC: 3534 AN: 5750

European-Non Finnish (NFE) AF: 0.486 AC: 537959 AN: 1107874

Other (OTH) AF: 0.544 AC: 32747 AN: 60146

GnomAD4 genome AF: 0.575 AC: 87403 AN: 151884 Hom.: 25701 Cov.: 31 AF XY: 0.584 AC XY: 43358 AN XY: 74232

African (AFR) AF: 0.654 AC: 27068 AN: 41408

American (AMR) AF: 0.639 AC: 9736 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2131 AN: 3468

East Asian (EAS) AF: 0.673 AC: 3471 AN: 5158

South Asian (SAS) AF: 0.697 AC: 3353 AN: 4810

European-Finnish (FIN) AF: 0.605 AC: 6367 AN: 10526

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33402 AN: 67958

Other (OTH) AF: 0.560 AC: 1182 AN: 2110

Alfa AF: 0.520 Hom.: 62752

Bravo AF: 0.581

TwinsUK AF: 0.482 AC: 1787

ALSPAC AF: 0.494 AC: 1904

ESP6500AA AF: 0.639 AC: 2815

ESP6500EA AF: 0.500 AC: 4301

ExAC AF: 0.570 AC: 69190

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.22
DANN	Benign	0.28
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.0030	T
MetaRNN	Benign	0.0000019	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.090	N
PhyloP100		-0.18
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.0070
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.036
MPC		0.017
ClinPred		0.00055	T
GERP RS		-0.22
Varity_R		0.12
gMVP		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs679620; hg19: chr11-102713620; COSMIC: COSV55405241; COSMIC: COSV55405241;