NM_002422.5:c.1334-382G>T

Variant names:

• chr11-102836608-C-A
• rs639752
• NM_002422.5:c.1334-382G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 42 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]

WTAPP1 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MMP3	NM_002422.5	c.1334-382G>T		intron_variant	Intron 9 of 9	ENST00000299855.10	NP_002413.1
WTAPP1	NR_038390.1	n.2484C>A		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.1334-382G>T		intron_variant	Intron 9 of 9	1	NM_002422.5	ENSP00000299855.5
WTAPP1	ENST00000525739.6	n.2484C>A		non_coding_transcript_exon_variant	Exon 8 of 8	2
MMP3	ENST00000434103.1	c.263-80G>T		intron_variant	Intron 2 of 2	3		ENSP00000398346.1

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

African (AFR) AF: 0.535 AC: 4689 AN: 8770

American (AMR) AF: 0.687 AC: 18692 AN: 27224

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 6594 AN: 10868

East Asian (EAS) AF: 0.672 AC: 6338 AN: 9432

South Asian (SAS) AF: 0.677 AC: 40200 AN: 59380

European-Finnish (FIN) AF: 0.588 AC: 16127 AN: 27408

Middle Eastern (MID) AF: 0.634 AC: 1761 AN: 2776

European-Non Finnish (NFE) AF: 0.489 AC: 78798 AN: 161196

Other (OTH) AF: 0.546 AC: 8019 AN: 14688

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

African (AFR) AF: 0.536 AC: 22150 AN: 41362

American (AMR) AF: 0.626 AC: 9556 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2128 AN: 3466

East Asian (EAS) AF: 0.675 AC: 3465 AN: 5134

South Asian (SAS) AF: 0.697 AC: 3345 AN: 4798

European-Finnish (FIN) AF: 0.607 AC: 6404 AN: 10558

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

European-Non Finnish (NFE) AF: 0.490 AC: 33304 AN: 67920

Other (OTH) AF: 0.534 AC: 1127 AN: 2110

Alfa AF: 0.525 Hom.: 4035

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
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs639752; hg19: chr11-102707339;