rs520540

Variant names:

• chr11-102838694-A-G
• rs520540
• NM_002422.5:c.1086T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-102838694-A-G
• chr11-102838694-A-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002422.5(MMP3):​c.1086T>C​(p.Ala362Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,611,212 control chromosomes in the GnomAD database, including 223,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23209 hom., cov: 32)
  • Exomes 𝑓: 0.52 (200076 hom.)
• Consequence: MMP3 NM_002422.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.523
• Publications: 58 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.072).
• BP6: Variant 11-102838694-A-G is Benign according to our data. Variant chr11-102838694-A-G is described in ClinVar as Benign. ClinVar VariationId is 403094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.523 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.679 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.1086T>C	p.Ala362Ala	synonymous	Exon 8 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.1086T>C	p.Ala362Ala	synonymous	Exon 8 of 10	ENSP00000299855.5	P08254
	MMP3	ENST00000434103.1	TSL:3	c.15T>C	p.Ala5Ala	synonymous	Exon 1 of 3	ENSP00000398346.1	H7C139

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83082 AN: 151760 Hom.: 23176 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.574 AC: 143760 AN: 250526 AF XY: 0.572

Gnomad AFR exome AF: 0.550

Gnomad AMR exome AF: 0.698

Gnomad ASJ exome AF: 0.606

Gnomad EAS exome AF: 0.668

Gnomad FIN exome AF: 0.602

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.518 AC: 756308 AN: 1459334 Hom.: 200076 Cov.: 37 AF XY: 0.523 AC XY: 380117 AN XY: 726138

African (AFR) AF: 0.552 AC: 18439 AN: 33390

American (AMR) AF: 0.689 AC: 30686 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 15863 AN: 26084

East Asian (EAS) AF: 0.682 AC: 27077 AN: 39692

South Asian (SAS) AF: 0.675 AC: 58097 AN: 86118

European-Finnish (FIN) AF: 0.595 AC: 31740 AN: 53334

Middle Eastern (MID) AF: 0.610 AC: 3513 AN: 5758

European-Non Finnish (NFE) AF: 0.485 AC: 538513 AN: 1110106

Other (OTH) AF: 0.537 AC: 32380 AN: 60310

GnomAD4 genome AF: 0.548 AC: 83166 AN: 151878 Hom.: 23209 Cov.: 32 AF XY: 0.557 AC XY: 41353 AN XY: 74198

African (AFR) AF: 0.553 AC: 22934 AN: 41444

American (AMR) AF: 0.629 AC: 9597 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2132 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3494 AN: 5158

South Asian (SAS) AF: 0.698 AC: 3347 AN: 4792

European-Finnish (FIN) AF: 0.620 AC: 6490 AN: 10474

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33340 AN: 67968

Other (OTH) AF: 0.539 AC: 1136 AN: 2108

Alfa AF: 0.512 Hom.: 9425

Bravo AF: 0.547

Asia WGS AF: 0.663 AC: 2304 AN: 3478

EpiCase AF: 0.498

EpiControl AF: 0.500

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
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		0.52
PromoterAI		0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs520540; hg19: chr11-102709425; COSMIC: COSV55406153; COSMIC: COSV55406153;