20-35274101-C-T

Position:

• chr20-35274101-C-T

Variant summary

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

The NM_006690.4(MMP24):​c.1601-171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,982 control chromosomes in the GnomAD database, including 3,799 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 0.22 (3799 hom., cov: 32)
• Consequence: MMP24 NM_006690.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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]

ENSG00000261582 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP24	NM_006690.4	c.1601-171C>T		intron_variant		ENST00000246186.8	NP_006681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP24	ENST00000246186.8	c.1601-171C>T		intron_variant		1	NM_006690.4	ENSP00000246186.6
ENSG00000261582	ENST00000444717.1	n.285-1956G>A		intron_variant		3		ENSP00000489186.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33257 AN: 151862 Hom.: 3789 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.219 AC: 33294 AN: 151982 Hom.: 3799 Cov.: 32 AF XY: 0.219 AC XY: 16300 AN XY: 74274

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.202

Alfa AF: 0.125 Hom.: 256

Bravo AF: 0.212

Asia WGS AF: 0.299 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs639763; hg19: chr20-33861904;