8-88081070-T-C

Variant names:

• chr8-88081070-T-C
• rs2664352
• NM_005941.5:c.1084-6327A>G

Variant summary

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

The NM_005941.5(MMP16):​c.1084-6327A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,742 control chromosomes in the GnomAD database, including 18,990 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 0.50 (18990 hom., cov: 31)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005941.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP16	NM_005941.5	MANE Select	c.1084-6327A>G		intron	N/A	NP_005932.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP16	ENST00000286614.11	TSL:1 MANE Select	c.1084-6327A>G		intron	N/A	ENSP00000286614.6
	MMP16	ENST00000544227.5	TSL:1	n.1084-6327A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75306 AN: 151622 Hom.: 18982 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.497 AC: 75350 AN: 151742 Hom.: 18990 Cov.: 31 AF XY: 0.498 AC XY: 36892 AN XY: 74134

African (AFR) AF: 0.550 AC: 22740 AN: 41376

American (AMR) AF: 0.474 AC: 7222 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1709 AN: 3468

East Asian (EAS) AF: 0.584 AC: 2961 AN: 5072

South Asian (SAS) AF: 0.403 AC: 1932 AN: 4800

European-Finnish (FIN) AF: 0.513 AC: 5402 AN: 10534

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.464 AC: 31525 AN: 67950

Other (OTH) AF: 0.509 AC: 1075 AN: 2114

Alfa AF: 0.473 Hom.: 52115

Bravo AF: 0.501

Asia WGS AF: 0.490 AC: 1703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		0.025
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: rs2664352; hg19: chr8-89093298;