chr8-88077054-G-A

Variant names:

• chr8-88077054-G-A
• rs2664349
• NM_005941.5:c.1084-2311C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005941.5(MMP16):​c.1084-2311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,092 control chromosomes in the GnomAD database, including 31,952 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 0.65 (31952 hom., cov: 32)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP16	NM_005941.5	c.1084-2311C>T		intron_variant	Intron 6 of 9	ENST00000286614.11	NP_005932.2
MMP16	XM_024447154.2	c.295-2311C>T		intron_variant	Intron 3 of 6		XP_024302922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP16	ENST00000286614.11	c.1084-2311C>T		intron_variant	Intron 6 of 9	1	NM_005941.5	ENSP00000286614.6
MMP16	ENST00000544227.5	n.1084-2311C>T		intron_variant	Intron 6 of 7	1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98288 AN: 151974 Hom.: 31931 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.647 AC: 98349 AN: 152092 Hom.: 31952 Cov.: 32 AF XY: 0.652 AC XY: 48448 AN XY: 74344

African (AFR) AF: 0.666 AC: 27647 AN: 41494

American (AMR) AF: 0.606 AC: 9255 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2135 AN: 3472

East Asian (EAS) AF: 0.771 AC: 3973 AN: 5154

South Asian (SAS) AF: 0.605 AC: 2921 AN: 4826

European-Finnish (FIN) AF: 0.728 AC: 7701 AN: 10582

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42430 AN: 67966

Other (OTH) AF: 0.662 AC: 1399 AN: 2112

Alfa AF: 0.633 Hom.: 23519

Bravo AF: 0.641

Asia WGS AF: 0.709 AC: 2464 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.59
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2664349; hg19: chr8-89089282;