Variant chr16-3050094-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_022468.5(MMP25):c.318C>T(p.Arg106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,610,944 control chromosomes in the GnomAD database, including 86,150 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 0.29 ( 6705 hom., cov: 33)

Exomes 𝑓: 0.33 ( 79445 hom. )

Consequence

MMP25
NM_022468.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.354

Variant links:

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]

MMP25 links:

MMP25-AS1 (HGNC:51372): (MMP25 antisense RNA 1)

MMP25-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP7

Synonymous conserved (PhyloP=0.354 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MMP25	NM_022468.5 linkuse as main transcript	c.318C>T	p.Arg106=	synonymous_variant	3/10	ENST00000336577.9	NP_071913.1
MMP25	XM_024450391.2 linkuse as main transcript	c.216C>T	p.Arg72=	synonymous_variant	2/9		XP_024306159.1
MMP25	XM_017023561.2 linkuse as main transcript	c.318C>T	p.Arg106=	synonymous_variant	3/6		XP_016879050.1
MMP25	XM_024450390.2 linkuse as main transcript	c.232+2547C>T		intron_variant			XP_024306158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP25	ENST00000336577.9 linkuse as main transcript	c.318C>T	p.Arg106=	synonymous_variant	3/10	1	NM_022468.5	ENSP00000337816	P1
MMP25-AS1	ENST00000576250.6 linkuse as main transcript	n.1110+1566G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43795

AN:

152022

Hom.:

6701

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.316

AC:

78339

AN:

248244

Hom.:

13032

AF XY:

0.312

AC XY:

42013

AN XY:

134600

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.423

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.195

Gnomad SAS exome

AF:

0.280

Gnomad FIN exome

AF:

0.253

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.323

GnomAD4 exome

AF:

0.326

AC:

476247

AN:

1458804

Hom.:

79445

Cov.:

AF XY:

0.325

AC XY:

236203

AN XY:

725778

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.412

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.287

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.337

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.288

AC:

43815

AN:

152140

Hom.:

6705

Cov.:

AF XY:

0.284

AC XY:

21109

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.379

Gnomad4 EAS

AF:

0.193

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.332

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.332

Hom.:

12653

Bravo

AF:

0.294

Asia WGS

AF:

0.210

AC:

731

AN:

3478

EpiCase

AF:

0.336

EpiControl

AF:

0.335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.5

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over