8-88060856-A-G

Variant summary

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

The NM_005941.5(MMP16):c.1223-4578T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,890 control chromosomes in the GnomAD database, including 4,676 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 0.23 (4676 hom., cov: 31)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP16	NM_005941.5	c.1223-4578T>C		intron_variant		ENST00000286614.11
MMP16	XM_024447154.2	c.434-4578T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP16	ENST00000286614.11	c.1223-4578T>C		intron_variant		1	NM_005941.5	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34682 AN: 151778 Hom.: 4662 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.229 AC: 34715 AN: 151890 Hom.: 4676 Cov.: 31 AF XY: 0.232 AC XY: 17195 AN XY: 74220

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.242

Alfa AF: 0.181 Hom.: 3601

Bravo AF: 0.254

Asia WGS AF: 0.296 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.3
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: rs1477908; hg19: chr8-89073084;