rs3739382

chr8-88074817-G-A

Variant summary

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

The NM_005941.5(MMP16):c.1084-74C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 1,506,114 control chromosomes in the GnomAD database, including 3,066 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 0.049 (292 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2774 hom.)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676

Genes affected

MMP16 (HGNC:7162): (matrix metallopeptidase 16) 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 MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The encoded protein activates MMP2 by cleavage. This gene was once referred to as MT-MMP2, but was renamed as MT-MMP3 or MMP16. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP16	NM_005941.5	c.1084-74C>T		intron_variant		ENST00000286614.11
MMP16	XM_024447154.2	c.295-74C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP16	ENST00000286614.11	c.1084-74C>T		intron_variant		1	NM_005941.5	P1
MMP16	ENST00000544227.5	n.1084-74C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7528 AN: 152054 Hom.: 293 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0522

GnomAD4 exome AF: 0.0558 AC: 75617 AN: 1353940 Hom.: 2774 AF XY: 0.0563 AC XY: 37752 AN XY: 671068

Gnomad4 AFR exome AF: 0.0193

Gnomad4 AMR exome AF: 0.0261

Gnomad4 ASJ exome AF: 0.0320

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.0651

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.0498

Gnomad4 OTH exome AF: 0.0623

GnomAD4 genome AF: 0.0494 AC: 7523 AN: 152174 Hom.: 292 Cov.: 32 AF XY: 0.0526 AC XY: 3913 AN XY: 74386

Gnomad4 AFR AF: 0.0202

Gnomad4 AMR AF: 0.0324

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.0690

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0491

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0528 Hom.: 37

Bravo AF: 0.0423

Asia WGS AF: 0.145 AC: 502 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.29
Dann	Benign	0.66

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: rs3739382; hg19: chr8-89087045; COSMIC: COSV54156174;