11-102868008-A-G

Position:

• chr11-102868008-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002426.6(MMP12):​c.687T>C​(p.Ser229=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000909 in 1,605,452 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00092 (7 hom.)
• Consequence: MMP12 NM_002426.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.517

Genes affected

MMP12 (HGNC:7158): (matrix metallopeptidase 12) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this 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. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease degrades soluble and insoluble elastin. This gene may play a role in aneurysm formation and mutations in this gene are associated with lung function and chronic obstructive pulmonary disease (COPD). This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 11-102868008-A-G is Benign according to our data. Variant chr11-102868008-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.517 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP12	NM_002426.6	c.687T>C	p.Ser229=	synonymous_variant	5/10	ENST00000571244.3	NP_002417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.687T>C	p.Ser229=	synonymous_variant	5/10	1	NM_002426.6	ENSP00000458585	P1

Frequencies

GnomAD3 genomes AF: 0.000821 AC: 125 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00130 AC: 304 AN: 233968 Hom.: 2 AF XY: 0.00129 AC XY: 162 AN XY: 126040

Gnomad AFR exome AF: 0.000140

Gnomad AMR exome AF: 0.000824

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000890

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.000919 AC: 1336 AN: 1453146 Hom.: 7 Cov.: 31 AF XY: 0.000970 AC XY: 700 AN XY: 721628

Gnomad4 AFR exome AF: 0.000749

Gnomad4 AMR exome AF: 0.000967

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00202

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000502

Gnomad4 OTH exome AF: 0.00198

GnomAD4 genome AF: 0.000814 AC: 124 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74472

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00158 Hom.: 5

Bravo AF: 0.000926

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

MMP12: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.7
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61730846; hg19: chr11-102738739;