8-88200229-A-G

Position:

• chr8-88200229-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.133-2923T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,666 control chromosomes in the GnomAD database, including 35,351 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 0.66 (35351 hom., cov: 30)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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]

MMP16 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP16	NM_005941.5	c.133-2923T>C		intron_variant		ENST00000286614.11	NP_005932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP16	ENST00000286614.11	c.133-2923T>C		intron_variant		1	NM_005941.5	ENSP00000286614.6
MMP16	ENST00000544227.5	n.133-2923T>C		intron_variant		1
MMP16	ENST00000522726.1	c.184-2923T>C		intron_variant		4		ENSP00000429147.1
MMP16	ENST00000520568.1	n.183-2923T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99739 AN: 151548 Hom.: 35361 Cov.: 30

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.658 AC: 99756 AN: 151666 Hom.: 35351 Cov.: 30 AF XY: 0.653 AC XY: 48439 AN XY: 74124

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.642

Alfa AF: 0.748 Hom.: 5556

Bravo AF: 0.624

Asia WGS AF: 0.519 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.79

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: rs13257117; hg19: chr8-89212458;