NM_002426.6:c.687T>C

Variant names:

• chr11-102868008-A-G
• rs61730846
• NM_002426.6:c.687T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002426.6(MMP12):​c.687T>C​(p.Ser229Ser) 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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002426.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP12	NM_002426.6	MANE Select	c.687T>C	p.Ser229Ser	synonymous	Exon 5 of 10	NP_002417.2	P39900

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP12	ENST00000571244.3	TSL:1 MANE Select	c.687T>C	p.Ser229Ser	synonymous	Exon 5 of 10	ENSP00000458585.1	P39900

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

GnomAD2 exomes AF: 0.00130 AC: 304 AN: 233968 AF XY: 0.00129

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 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

African (AFR) AF: 0.000749 AC: 25 AN: 33376

American (AMR) AF: 0.000967 AC: 42 AN: 43446

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 321 AN: 25902

East Asian (EAS) AF: 0.00 AC: 0 AN: 39482

South Asian (SAS) AF: 0.00202 AC: 170 AN: 84072

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53052

Middle Eastern (MID) AF: 0.0177 AC: 102 AN: 5762

European-Non Finnish (NFE) AF: 0.000502 AC: 556 AN: 1107902

Other (OTH) AF: 0.00198 AC: 119 AN: 60152

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

African (AFR) AF: 0.000265 AC: 11 AN: 41570

American (AMR) AF: 0.000915 AC: 14 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00147 Hom.: 5

Bravo AF: 0.000926

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.7
DANN	Benign	0.50
PhyloP100		0.52

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

Other links and lift over

dbSNP: rs61730846; hg19: chr11-102738739;