20-35261376-G-A

Variant names:

• chr20-35261376-G-A
• rs1555322
• NM_006690.4:c.818-2415G>A

Variant summary

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

The NM_006690.4(MMP24):​c.818-2415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,172 control chromosomes in the GnomAD database, including 1,498 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1498 hom., cov: 32)
• Consequence: MMP24 NM_006690.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811
• Publications: 30 publications found

Genes affected

MMP24 (HGNC:7172): (matrix metallopeptidase 24) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this 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 protease. Unlike most MMPs, which are secreted, this protease is a member of the membrane-type MMP (MT-MMP) subfamily, contains a transmembrane domain and is expressed at the cell surface. Substrates of this protease include the proteins cadherin 2 and matrix metallopeptidase 2 (also known as 72 kDa type IV collagenase). The gene has previously been referred to as MMP25 but has been renamed matrix metallopeptidase 24 (MMP24). [provided by RefSeq, Oct 2019]

MMP24-AS1-EDEM2 (HGNC:):

MMP24OS (HGNC:44421): (MMP24 opposite strand)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006690.4. 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
	MMP24	NM_006690.4	MANE Select	c.818-2415G>A		intron	N/A	NP_006681.1
	MMP24-AS1-EDEM2	NM_001355008.2		c.-463+10629C>T		intron	N/A	NP_001341937.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP24	ENST00000246186.8	TSL:1 MANE Select	c.818-2415G>A		intron	N/A	ENSP00000246186.6
	MMP24OS	ENST00000433764.5	TSL:4	n.221+10629C>T		intron	N/A
	MMP24OS	ENST00000438751.5	TSL:3	n.237+10629C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20758 AN: 152054 Hom.: 1496 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20765 AN: 152172 Hom.: 1498 Cov.: 32 AF XY: 0.134 AC XY: 9977 AN XY: 74398

African (AFR) AF: 0.159 AC: 6594 AN: 41504

American (AMR) AF: 0.105 AC: 1612 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.107 AC: 552 AN: 5182

South Asian (SAS) AF: 0.165 AC: 799 AN: 4830

European-Finnish (FIN) AF: 0.130 AC: 1371 AN: 10586

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8929 AN: 67994

Other (OTH) AF: 0.125 AC: 265 AN: 2112

Alfa AF: 0.131 Hom.: 3098

Bravo AF: 0.134

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.095
DANN	Benign	0.69
PhyloP100		-0.81
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: rs1555322; hg19: chr20-33849179;