8-88063751-T-C

Position:

• chr8-88063751-T-C

Variant summary

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

The NM_005941.5(MMP16):​c.1223-7473A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,782 control chromosomes in the GnomAD database, including 20,774 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 0.52 (20774 hom., cov: 31)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP16	NM_005941.5	c.1223-7473A>G		intron_variant		ENST00000286614.11	NP_005932.2
MMP16	XM_024447154.2	c.434-7473A>G		intron_variant			XP_024302922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP16	ENST00000286614.11	c.1223-7473A>G		intron_variant		1	NM_005941.5	ENSP00000286614	P1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78708 AN: 151664 Hom.: 20755 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.519 AC: 78764 AN: 151782 Hom.: 20774 Cov.: 31 AF XY: 0.522 AC XY: 38728 AN XY: 74174

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.539

Alfa AF: 0.495 Hom.: 8438

Bravo AF: 0.527

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
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: rs1824717; hg19: chr8-89075979;