16-3060713-C-T

Position:

• chr16-3060713-C-T

Variant summary

Our verdict is Benign. Variant got -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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MMP25	NM_022468.5	c.*1615C>T		3_prime_UTR_variant	10/10	ENST00000336577.9	NP_071913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP25	ENST00000336577.9	c.*1615C>T		3_prime_UTR_variant	10/10	1	NM_022468.5	ENSP00000337816	P1
MMP25	ENST00000612971.2	c.*2845C>T		3_prime_UTR_variant, NMD_transcript_variant	11/11	5		ENSP00000482854

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 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0681

Gnomad4 FIN AF: 0.0397

Gnomad4 NFE AF: 0.0980

Gnomad4 OTH AF: 0.115

Alfa AF: 0.106 Hom.: 1048

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

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;