rs569444

chr11-102836574-G-Achr11-102836574-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002422.5(MMP3):c.1334-348C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 485,038 control chromosomes in the GnomAD database, including 4,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1229 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3211 hom.)
• Consequence: MMP3 NM_002422.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.607

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-102836574-G-A is Benign according to our data. Variant chr11-102836574-G-A is described in ClinVar as [Benign]. Clinvar id is 1263820.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.1334-348C>T		intron_variant		ENST00000299855.10
WTAPP1	NR_038390.1	n.2450G>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP3	ENST00000299855.10	c.1334-348C>T		intron_variant		1	NM_002422.5	P1
MMP3	ENST00000434103.1	c.265-46C>T		intron_variant		3
WTAPP1	ENST00000525739.6	n.2450G>A		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15855 AN: 151982 Hom.: 1229 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.0781

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.120 AC: 18070 AN: 150284 Hom.: 1438 AF XY: 0.119 AC XY: 9545 AN XY: 80504

Gnomad AFR exome AF: 0.0203

Gnomad AMR exome AF: 0.0748

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.0712

Gnomad SAS exome AF: 0.0820

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.127 AC: 42184 AN: 332938 Hom.: 3211 Cov.: 0 AF XY: 0.124 AC XY: 23162 AN XY: 187376

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.0746

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.0838

Gnomad4 SAS exome AF: 0.0849

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.104 AC: 15855 AN: 152100 Hom.: 1229 Cov.: 32 AF XY: 0.108 AC XY: 8057 AN XY: 74322

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.0838

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0719

Gnomad4 SAS AF: 0.0786

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.103

Alfa AF: 0.122 Hom.: 279

Bravo AF: 0.0873

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.70
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs569444; hg19: chr11-102707305; COSMIC: COSV55406321; COSMIC: COSV55406321;