NM_005940.5:c.29C>G

Variant names:

• chr22-23772899-C-G
• rs1927281213
• NM_005940.5:c.29C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005940.5(MMP11):​c.29C>G​(p.Ala10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 150,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP11 NM_005940.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.250
• Publications: 0 publications found

Genes affected

MMP11 (HGNC:7157): (matrix metallopeptidase 11) 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. However, the enzyme encoded by this gene is activated intracellularly by furin within the constitutive secretory pathway. Also in contrast to other MMP's, this enzyme cleaves alpha 1-proteinase inhibitor but weakly degrades structural proteins of the extracellular matrix. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10680437).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005940.5. 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
	MMP11	NM_005940.5	MANE Select	c.29C>G	p.Ala10Gly	missense	Exon 1 of 8	NP_005931.2	P24347
	MMP11	NR_133013.2		n.51C>G		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP11	ENST00000215743.8	TSL:1 MANE Select	c.29C>G	p.Ala10Gly	missense	Exon 1 of 8	ENSP00000215743.3	P24347
	MMP11	ENST00000872484.1		c.29C>G	p.Ala10Gly	missense	Exon 1 of 8	ENSP00000542543.1
	MMP11	ENST00000872487.1		c.29C>G	p.Ala10Gly	missense	Exon 1 of 8	ENSP00000542546.1

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150848 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1019354 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 482390

African (AFR) AF: 0.00 AC: 0 AN: 20478

American (AMR) AF: 0.00 AC: 0 AN: 6690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11518

East Asian (EAS) AF: 0.00 AC: 0 AN: 20042

South Asian (SAS) AF: 0.00 AC: 0 AN: 19664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 881344

Other (OTH) AF: 0.00 AC: 0 AN: 38888

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 150956 Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1 AN XY: 73770

African (AFR) AF: 0.00 AC: 0 AN: 41416

American (AMR) AF: 0.0000659 AC: 1 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67516

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.13	N
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.25
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.019
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.23		Gain of loop (P = 0.0321)
MVP		0.35
MPC		0.32
ClinPred		0.40	T
GERP RS		1.0
PromoterAI		-0.037	Neutral
Varity_R		0.17
gMVP		0.48
Mutation Taster		=95/5	polymorphism

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: rs1927281213; hg19: chr22-24115086;