NM_021801.5:c.780A>G

Variant names:

• chr11-4992236-A-G
• rs16908114
• NM_021801.5:c.780A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021801.5(MMP26):​c.780A>G​(p.Ile260Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,610,454 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.018 (83 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (84 hom.)
• Consequence: MMP26 NM_021801.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 8 publications found

Genes affected

MMP26 (HGNC:14249): (matrix metallopeptidase 26) 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. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037540793).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021801.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP26	NM_021801.5	MANE Select	c.780A>G	p.Ile260Met	missense	Exon 8 of 8	NP_068573.2
	MMP26	NM_001384608.1		c.570A>G	p.Ile190Met	missense	Exon 8 of 8	NP_001371537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP26	ENST00000380390.6	TSL:5 MANE Select	c.780A>G	p.Ile260Met	missense	Exon 8 of 8	ENSP00000369753.1
	MMP26	ENST00000300762.2	TSL:1	c.570A>G	p.Ile190Met	missense	Exon 8 of 8	ENSP00000300762.2
	MMP26	ENST00000690848.1		c.780A>G	p.Ile260Met	missense	Exon 7 of 7	ENSP00000510347.1

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2782 AN: 151692 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00684

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00480 AC: 1172 AN: 244120 AF XY: 0.00330

Gnomad AFR exome AF: 0.0677

Gnomad AMR exome AF: 0.00265

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000165

Gnomad OTH exome AF: 0.00236

GnomAD4 exome AF: 0.00175 AC: 2550 AN: 1458644 Hom.: 84 Cov.: 32 AF XY: 0.00151 AC XY: 1096 AN XY: 725560

African (AFR) AF: 0.0627 AC: 2090 AN: 33326

American (AMR) AF: 0.00287 AC: 127 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.000116 AC: 10 AN: 85850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53050

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5756

European-Non Finnish (NFE) AF: 0.0000693 AC: 77 AN: 1110472

Other (OTH) AF: 0.00389 AC: 234 AN: 60214

GnomAD4 genome AF: 0.0184 AC: 2793 AN: 151810 Hom.: 83 Cov.: 32 AF XY: 0.0181 AC XY: 1339 AN XY: 74164

African (AFR) AF: 0.0640 AC: 2646 AN: 41368

American (AMR) AF: 0.00683 AC: 104 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67952

Other (OTH) AF: 0.0138 AC: 29 AN: 2106

Alfa AF: 0.00672 Hom.: 67

Bravo AF: 0.0211

ESP6500AA AF: 0.0652 AC: 287

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00588 AC: 714

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.054
DANN	Benign	0.059
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00021	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.060	N
PhyloP100		-1.7
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.89	N
REVEL	Benign	0.082
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.036
MVP		0.092
MPC		0.070
ClinPred		0.0033	T
GERP RS		-2.3
Varity_R		0.036
gMVP		0.17
Mutation Taster		=100/0	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: rs16908114; hg19: chr11-5013466;