rs639752

chr11-102836608-C-Achr11-102836608-C-T

Variant summary

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

The NM_002422.5(MMP3):c.1334-382G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 473,550 control chromosomes in the GnomAD database, including 74,912 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 0.54 (22613 hom., cov: 30)
  • Exomes 𝑓: 0.56 (52299 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP3	NM_002422.5	c.1334-382G>T		intron_variant		ENST00000299855.10
WTAPP1	NR_038390.1	n.2484C>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP3	ENST00000299855.10	c.1334-382G>T		intron_variant		1	NM_002422.5	P1
MMP3	ENST00000434103.1	c.265-80G>T		intron_variant		3
WTAPP1	ENST00000525739.6	n.2484C>A		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82092 AN: 151688 Hom.: 22579 Cov.: 30

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.563 AC: 181218 AN: 321742 Hom.: 52299 Cov.: 0 AF XY: 0.572 AC XY: 103723 AN XY: 181276

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.687

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.672

Gnomad4 SAS exome AF: 0.677

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.546

GnomAD4 genome AF: 0.541 AC: 82177 AN: 151808 Hom.: 22613 Cov.: 30 AF XY: 0.551 AC XY: 40871 AN XY: 74210

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.534

Alfa AF: 0.525 Hom.: 3936

Bravo AF: 0.542

Asia WGS AF: 0.661 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.92
Dann	Benign	0.49

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: rs639752; hg19: chr11-102707339;