rs1345948587

Variant names:

• chr22-23772875-C-A
• rs1345948587
• NM_005940.5:c.5C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-23772875-C-A
• chr22-23772875-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005940.5(MMP11):​c.5C>A​(p.Ala2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,158,206 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: MMP11 NM_005940.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.289
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26241362).

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.5C>A	p.Ala2Asp	missense	Exon 1 of 8	NP_005931.2	P24347
	MMP11	NR_133013.2		n.27C>A		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.5C>A	p.Ala2Asp	missense	Exon 1 of 8	ENSP00000215743.3	P24347
	MMP11	ENST00000872484.1		c.5C>A	p.Ala2Asp	missense	Exon 1 of 8	ENSP00000542543.1
	MMP11	ENST00000872487.1		c.5C>A	p.Ala2Asp	missense	Exon 1 of 8	ENSP00000542546.1

Frequencies

GnomAD3 genomes AF: 0.0000728 AC: 11 AN: 151178 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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 AF: 0.00000794 AC: 8 AN: 1007028 Hom.: 0 Cov.: 28 AF XY: 0.00000632 AC XY: 3 AN XY: 474796

African (AFR) AF: 0.000396 AC: 8 AN: 20194

American (AMR) AF: 0.00 AC: 0 AN: 6016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11034

East Asian (EAS) AF: 0.00 AC: 0 AN: 19176

South Asian (SAS) AF: 0.00 AC: 0 AN: 18900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2522

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 873482

Other (OTH) AF: 0.00 AC: 0 AN: 38234

GnomAD4 genome AF: 0.0000728 AC: 11 AN: 151178 Hom.: 0 Cov.: 31 AF XY: 0.0000948 AC XY: 7 AN XY: 73806

African (AFR) AF: 0.000266 AC: 11 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67672

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ClinVar

ClinVar submissions as Germline

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	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.35	N
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.29
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.58	P
Vest4		0.32
MutPred		0.18		Loss of MoRF binding (P = 0.0116)
MVP		0.68
MPC		0.48
ClinPred		0.96	D
GERP RS		2.1
PromoterAI		0.38	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.36
gMVP		0.69
Mutation Taster		=83/17	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: rs1345948587; hg19: chr22-24115062;