22-23779191-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A38T) has been classified as Likely benign.

• 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
• Publications: 52 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: Benign. The variant received -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

GnomAD2 exomes AF: 0.838 AC: 179153 AN: 213824 AF XY: 0.841

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 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

African (AFR) AF: 0.557 AC: 18412 AN: 33084

American (AMR) AF: 0.826 AC: 35118 AN: 42508

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 22191 AN: 25602

East Asian (EAS) AF: 0.663 AC: 25720 AN: 38804

South Asian (SAS) AF: 0.738 AC: 61591 AN: 83446

European-Finnish (FIN) AF: 0.935 AC: 44052 AN: 47110

Middle Eastern (MID) AF: 0.858 AC: 4928 AN: 5742

European-Non Finnish (NFE) AF: 0.920 AC: 1013983 AN: 1102516

Other (OTH) AF: 0.865 AC: 51522 AN: 59596

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

African (AFR) AF: 0.573 AC: 23750 AN: 41444

American (AMR) AF: 0.850 AC: 13009 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3029 AN: 3462

East Asian (EAS) AF: 0.697 AC: 3596 AN: 5162

South Asian (SAS) AF: 0.706 AC: 3407 AN: 4824

European-Finnish (FIN) AF: 0.938 AC: 9960 AN: 10614

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62360 AN: 67988

Other (OTH) AF: 0.807 AC: 1701 AN: 2108

Alfa AF: 0.873 Hom.: 189350

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
PhyloP100		0.35
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
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs738792; hg19: chr22-24121378; COSMIC: COSV53155825; COSMIC: COSV53155825;