8-88256314-T-G

Variant names:

• chr8-88256314-T-G
• rs6994019
• NM_005941.5:c.133-59008A>C

Variant summary

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

The NM_005941.5(MMP16):​c.133-59008A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,014 control chromosomes in the GnomAD database, including 31,335 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 0.61 (31335 hom., cov: 32)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 18 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP16	NM_005941.5	c.133-59008A>C		intron_variant	Intron 1 of 9	ENST00000286614.11	NP_005932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP16	ENST00000286614.11	c.133-59008A>C		intron_variant	Intron 1 of 9	1	NM_005941.5	ENSP00000286614.6
MMP16	ENST00000544227.5	n.133-59008A>C		intron_variant	Intron 1 of 7	1
MMP16	ENST00000522726.1	c.184-59008A>C		intron_variant	Intron 2 of 4	4		ENSP00000429147.1
MMP16	ENST00000520568.1	n.183-59008A>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92868 AN: 151896 Hom.: 31332 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.611 AC: 92886 AN: 152014 Hom.: 31335 Cov.: 32 AF XY: 0.617 AC XY: 45802 AN XY: 74280

African (AFR) AF: 0.304 AC: 12613 AN: 41468

American (AMR) AF: 0.722 AC: 11025 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2299 AN: 3472

East Asian (EAS) AF: 0.904 AC: 4649 AN: 5144

South Asian (SAS) AF: 0.598 AC: 2891 AN: 4834

European-Finnish (FIN) AF: 0.776 AC: 8184 AN: 10548

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.723 AC: 49177 AN: 67972

Other (OTH) AF: 0.607 AC: 1283 AN: 2112

Alfa AF: 0.692 Hom.: 160749

Bravo AF: 0.602

Asia WGS AF: 0.640 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.57
PhyloP100		-0.24
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: rs6994019; hg19: chr8-89268543;