rs563096

Positions:

• chr11-102836635-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002422.5(MMP3):​c.1334-409T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 460,442 control chromosomes in the GnomAD database, including 4,189 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 0.10 (1233 hom., cov: 32)
  • Exomes 𝑓: 0.13 (2956 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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]

WTAPP1 (HGNC:44115): (WTAP pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP3	NM_002422.5	c.1334-409T>A		intron_variant		ENST00000299855.10
WTAPP1	NR_038390.1	n.2511A>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP3	ENST00000299855.10	c.1334-409T>A		intron_variant		1	NM_002422.5	P1
MMP3	ENST00000434103.1	c.265-107T>A		intron_variant		3
WTAPP1	ENST00000525739.6	n.2511A>T		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15857 AN: 151922 Hom.: 1233 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.126 AC: 38926 AN: 308402 Hom.: 2956 Cov.: 0 AF XY: 0.123 AC XY: 21283 AN XY: 173346

Gnomad4 AFR exome AF: 0.0238

Gnomad4 AMR exome AF: 0.0738

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0803

Gnomad4 SAS exome AF: 0.0849

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.104 AC: 15857 AN: 152040 Hom.: 1233 Cov.: 32 AF XY: 0.108 AC XY: 8059 AN XY: 74288

Gnomad4 AFR AF: 0.0246

Gnomad4 AMR AF: 0.0841

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0725

Gnomad4 SAS AF: 0.0792

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.103

Alfa AF: 0.124 Hom.: 184

Bravo AF: 0.0873

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs563096; hg19: chr11-102707366; COSMIC: COSV55407393; COSMIC: COSV55407393;