16-3060713-C-T

Variant names:

• chr16-3060713-C-T
• rs10438593
• NM_022468.5:c.*1615C>T

Variant summary

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

The NM_022468.5(MMP25):​c.*1615C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,210 control chromosomes in the GnomAD database, including 1,446 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 0.12 (1446 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP25 NM_022468.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

Genes affected

MMP25 (HGNC:14246): (matrix metallopeptidase 25) 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 MMPs are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily, attached to the plasma membrane via a glycosylphosphatidyl inositol anchor. In response to bacterial infection or inflammation, the encoded protein is thought to inactivate alpha-1 proteinase inhibitor, a major tissue protectant against proteolytic enzymes released by activated neutrophils, facilitating the transendothelial migration of neutrophils to inflammatory sites. The encoded protein may also play a role in tumor invasion and metastasis through activation of MMP2. The gene has previously been referred to as MMP20 but has been renamed MMP25. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP25	NM_022468.5	c.*1615C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000336577.9	NP_071913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP25	ENST00000336577.9	c.*1615C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_022468.5	ENSP00000337816.4
MMP25	ENST00000612971.2	n.*2845C>T		non_coding_transcript_exon_variant	Exon 11 of 11	5		ENSP00000482854.2
MMP25	ENST00000612971.2	n.*2845C>T		3_prime_UTR_variant	Exon 11 of 11	5		ENSP00000482854.2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18351 AN: 152092 Hom.: 1440 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0664

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.117

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 AFR exome AC: 0 AN: 0

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AC: 0 AN: 0

Gnomad4 SAS exome AC: 0 AN: 0

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 2

Gnomad4 NFE exome AF: 0.00 AC: 0 AN: 2

Gnomad4 Remaining exome AC: 0 AN: 0

GnomAD4 genome AF: 0.121 AC: 18392 AN: 152210 Hom.: 1446 Cov.: 33 AF XY: 0.116 AC XY: 8619 AN XY: 74424

Gnomad4 AFR AF: 0.205 AC: 0.204879 AN: 0.204879

Gnomad4 AMR AF: 0.102 AC: 0.10208 AN: 0.10208

Gnomad4 ASJ AF: 0.155 AC: 0.155242 AN: 0.155242

Gnomad4 EAS AF: 0.00135 AC: 0.00134927 AN: 0.00134927

Gnomad4 SAS AF: 0.0681 AC: 0.0681159 AN: 0.0681159

Gnomad4 FIN AF: 0.0397 AC: 0.0397095 AN: 0.0397095

Gnomad4 NFE AF: 0.0980 AC: 0.0979939 AN: 0.0979939

Gnomad4 OTH AF: 0.115 AC: 0.11491 AN: 0.11491

Alfa AF: 0.107 Hom.: 1591

Bravo AF: 0.127

Asia WGS AF: 0.0400 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.7
DANN	Benign	0.55
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

Publications

LitVar

Other links and lift over

dbSNP: rs10438593; hg19: chr16-3110714;