16-3050094-C-T

Variant names:

• chr16-3050094-C-T
• rs10431961
• NM_022468.5:c.318C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022468.5(MMP25):​c.318C>T​(p.Arg106Arg) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354
• Publications: 33 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MMP25	NM_022468.5	c.318C>T	p.Arg106Arg	synonymous_variant	Exon 3 of 10	ENST00000336577.9	NP_071913.1
MMP25	XM_024450391.2	c.216C>T	p.Arg72Arg	synonymous_variant	Exon 2 of 9		XP_024306159.1
MMP25	XM_017023561.2	c.318C>T	p.Arg106Arg	synonymous_variant	Exon 3 of 6		XP_016879050.1
MMP25	XM_024450390.2	c.232+2547C>T		intron_variant	Intron 2 of 7		XP_024306158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP25	ENST00000336577.9	c.318C>T	p.Arg106Arg	synonymous_variant	Exon 3 of 10	1	NM_022468.5	ENSP00000337816.4

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43795 AN: 152022 Hom.: 6701 Cov.: 33

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

GnomAD2 exomes AF: 0.316 AC: 78339 AN: 248244 AF XY: 0.312

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 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.: 46 AF XY: 0.325 AC XY: 236203 AN XY: 725778

African (AFR) AF: 0.205 AC: 6851 AN: 33470

American (AMR) AF: 0.412 AC: 18400 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 9241 AN: 26096

East Asian (EAS) AF: 0.212 AC: 8413 AN: 39674

South Asian (SAS) AF: 0.287 AC: 24756 AN: 86212

European-Finnish (FIN) AF: 0.262 AC: 13308 AN: 50884

Middle Eastern (MID) AF: 0.354 AC: 2041 AN: 5764

European-Non Finnish (NFE) AF: 0.337 AC: 374743 AN: 1111656

Other (OTH) AF: 0.306 AC: 18494 AN: 60360

GnomAD4 genome AF: 0.288 AC: 43815 AN: 152140 Hom.: 6705 Cov.: 33 AF XY: 0.284 AC XY: 21109 AN XY: 74370

African (AFR) AF: 0.209 AC: 8677 AN: 41512

American (AMR) AF: 0.347 AC: 5303 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3472

East Asian (EAS) AF: 0.193 AC: 1001 AN: 5174

South Asian (SAS) AF: 0.269 AC: 1299 AN: 4826

European-Finnish (FIN) AF: 0.245 AC: 2594 AN: 10604

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.332 AC: 22588 AN: 67958

Other (OTH) AF: 0.289 AC: 610 AN: 2112

Alfa AF: 0.326 Hom.: 16457

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
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10431961; hg19: chr16-3100095; COSMIC: COSV60678630; COSMIC: COSV60678630;