11-102842716-G-C

Variant names:

• chr11-102842716-G-C
• rs41380244
• NM_002422.5:c.306C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002422.5(MMP3):​c.306C>G​(p.Thr102Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,613,822 control chromosomes in the GnomAD database, including 6,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (603 hom., cov: 30)
  • Exomes 𝑓: 0.086 (5738 hom.)
• Consequence: MMP3 NM_002422.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.681
• Publications: 18 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-102842716-G-C is Benign according to our data. Variant chr11-102842716-G-C is described in ClinVar as Benign. ClinVar VariationId is 403096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.681 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP3	NM_002422.5	c.306C>G	p.Thr102Thr	synonymous_variant	Exon 2 of 10	ENST00000299855.10	NP_002413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP3	ENST00000299855.10	c.306C>G	p.Thr102Thr	synonymous_variant	Exon 2 of 10	1	NM_002422.5	ENSP00000299855.5
MMP3	ENST00000524478.1	n.*148C>G		non_coding_transcript_exon_variant	Exon 2 of 4	4		ENSP00000435255.1
MMP3	ENST00000524478.1	n.*148C>G		3_prime_UTR_variant	Exon 2 of 4	4		ENSP00000435255.1

Frequencies

GnomAD3 genomes AF: 0.0874 AC: 13286 AN: 152036 Hom.: 602 Cov.: 30

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0707

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0924

Gnomad OTH AF: 0.0855

GnomAD2 exomes AF: 0.0760 AC: 19075 AN: 251098 AF XY: 0.0778

Gnomad AFR exome AF: 0.0992

Gnomad AMR exome AF: 0.0474

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.00256

Gnomad FIN exome AF: 0.0644

Gnomad NFE exome AF: 0.0913

Gnomad OTH exome AF: 0.0869

GnomAD4 exome AF: 0.0861 AC: 125798 AN: 1461668 Hom.: 5738 Cov.: 57 AF XY: 0.0862 AC XY: 62699 AN XY: 727110

African (AFR) AF: 0.100 AC: 3352 AN: 33464

American (AMR) AF: 0.0500 AC: 2232 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 3478 AN: 26132

East Asian (EAS) AF: 0.00116 AC: 46 AN: 39694

South Asian (SAS) AF: 0.0700 AC: 6037 AN: 86248

European-Finnish (FIN) AF: 0.0666 AC: 3555 AN: 53406

Middle Eastern (MID) AF: 0.128 AC: 739 AN: 5768

European-Non Finnish (NFE) AF: 0.0909 AC: 101074 AN: 1111898

Other (OTH) AF: 0.0875 AC: 5285 AN: 60378

GnomAD4 genome AF: 0.0874 AC: 13297 AN: 152154 Hom.: 603 Cov.: 30 AF XY: 0.0859 AC XY: 6385 AN XY: 74372

African (AFR) AF: 0.100 AC: 4151 AN: 41506

American (AMR) AF: 0.0706 AC: 1078 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 462 AN: 3460

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5184

South Asian (SAS) AF: 0.0666 AC: 321 AN: 4820

European-Finnish (FIN) AF: 0.0592 AC: 627 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0923 AC: 6279 AN: 67994

Other (OTH) AF: 0.0851 AC: 180 AN: 2116

Alfa AF: 0.0521 Hom.: 66

Bravo AF: 0.0880

EpiCase AF: 0.0946

EpiControl AF: 0.0967

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.86
CADD	Benign	0.30
DANN	Benign	0.30
PhyloP100		-0.68
Mutation Taster		=97/3	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: rs41380244; hg19: chr11-102713447; COSMIC: COSV55406371; COSMIC: COSV55406371;