rs738792

Variant names:

• chr22-23779191-C-T
• rs738792
• NM_005940.5:c.113C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005940.5(MMP11):​c.113C>T​(p.Ala38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 1,590,512 control chromosomes in the GnomAD database, including 622,731 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.80 (50485 hom., cov: 32)
  • Exomes 𝑓: 0.89 (572246 hom.)
• Consequence: MMP11 NM_005940.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1547959E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP11	NM_005940.5	c.113C>T	p.Ala38Val	missense_variant	Exon 2 of 8	ENST00000215743.8	NP_005931.2
MMP11	NR_133013.2	n.135C>T		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP11	ENST00000215743.8	c.113C>T	p.Ala38Val	missense_variant	Exon 2 of 8	1	NM_005940.5	ENSP00000215743.3

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121792 AN: 151986 Hom.: 50491 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.816

GnomAD3 exomes AF: 0.838 AC: 179153 AN: 213824 Hom.: 76325 AF XY: 0.841 AC XY: 97903 AN XY: 116400

Gnomad AFR exome AF: 0.552

Gnomad AMR exome AF: 0.821

Gnomad ASJ exome AF: 0.868

Gnomad EAS exome AF: 0.695

Gnomad SAS exome AF: 0.733

Gnomad FIN exome AF: 0.936

Gnomad NFE exome AF: 0.918

Gnomad OTH exome AF: 0.862

GnomAD4 exome AF: 0.888 AC: 1277517 AN: 1438408 Hom.: 572246 Cov.: 43 AF XY: 0.885 AC XY: 631626 AN XY: 713842

Gnomad4 AFR exome AF: 0.557

Gnomad4 AMR exome AF: 0.826

Gnomad4 ASJ exome AF: 0.867

Gnomad4 EAS exome AF: 0.663

Gnomad4 SAS exome AF: 0.738

Gnomad4 FIN exome AF: 0.935

Gnomad4 NFE exome AF: 0.920

Gnomad4 OTH exome AF: 0.865

GnomAD4 genome AF: 0.801 AC: 121811 AN: 152104 Hom.: 50485 Cov.: 32 AF XY: 0.801 AC XY: 59553 AN XY: 74346

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.938

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.807

Alfa AF: 0.895 Hom.: 119902

Bravo AF: 0.786

TwinsUK AF: 0.929 AC: 3444

ALSPAC AF: 0.921 AC: 3549

ESP6500AA AF: 0.580 AC: 2539

ESP6500EA AF: 0.916 AC: 7867

ExAC AF: 0.822 AC: 98276

Asia WGS AF: 0.688 AC: 2391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.0
DANN	Benign	0.92
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.080	N
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.81	L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.062
Sift	Benign	0.33	T
Sift4G	Benign	0.57	T
Polyphen		0.099	B
Vest4		0.068
MPC		0.32
ClinPred		0.0031	T
GERP RS		0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.031
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs738792; hg19: chr22-24121378; COSMIC: COSV53155825; COSMIC: COSV53155825;