Variant 11-102840607-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000299855.10(MMP3):c.626-14A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,611,110 control chromosomes in the GnomAD database, including 226,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25211 hom., cov: 32)

Exomes 𝑓: 0.52 ( 201738 hom. )

Consequence

MMP3
ENST00000299855.10 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.986

Variant links:

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]

MMP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-102840607-T-C is Benign according to our data. Variant chr11-102840607-T-C is described in ClinVar as [Benign]. Clinvar id is 403095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP3	NM_002422.5 linkuse as main transcript	c.626-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10 linkuse as main transcript	c.626-14A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002422.5	ENSP00000299855	P1

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86588

AN:

151908

Hom.:

25173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.634

Gnomad AMI

AF:

0.585

Gnomad AMR

AF:

0.636

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.675

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.579

AC:

144750

AN:

249956

Hom.:

42969

AF XY:

0.576

AC XY:

77797

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.634

Gnomad AMR exome

AF:

0.701

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.667

Gnomad SAS exome

AF:

0.674

Gnomad FIN exome

AF:

0.590

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.552

GnomAD4 exome

AF:

0.521

AC:

759735

AN:

1459086

Hom.:

201738

Cov.:

AF XY:

0.526

AC XY:

381501

AN XY:

725928

show subpopulations

Gnomad4 AFR exome

AF:

0.639

Gnomad4 AMR exome

AF:

0.693

Gnomad4 ASJ exome

AF:

0.609

Gnomad4 EAS exome

AF:

0.682

Gnomad4 SAS exome

AF:

0.674

Gnomad4 FIN exome

AF:

0.585

Gnomad4 NFE exome

AF:

0.486

Gnomad4 OTH exome

AF:

0.543

GnomAD4 genome

AF:

0.570

AC:

86681

AN:

152024

Hom.:

25211

Cov.:

AF XY:

0.579

AC XY:

43021

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.634

Gnomad4 AMR

AF:

0.636

Gnomad4 ASJ

AF:

0.615

Gnomad4 EAS

AF:

0.675

Gnomad4 SAS

AF:

0.697

Gnomad4 FIN

AF:

0.606

Gnomad4 NFE

AF:

0.492

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.535

Hom.:

4931

Bravo

AF:

0.574

Asia WGS

AF:

0.665

AC:

2313

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.5

DANN

Benign

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over