8-88077198-T-C

Variant names:

• chr8-88077198-T-C
• rs10504853
• NM_005941.5:c.1084-2455A>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.1084-2455A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,222 control chromosomes in the GnomAD database, including 2,477 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 0.17 (2477 hom., cov: 33)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP16	NM_005941.5	MANE Select	c.1084-2455A>G		intron	N/A	NP_005932.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP16	ENST00000286614.11	TSL:1 MANE Select	c.1084-2455A>G		intron	N/A	ENSP00000286614.6
	MMP16	ENST00000544227.5	TSL:1	n.1084-2455A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25467 AN: 152104 Hom.: 2473 Cov.: 33

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.167 AC: 25485 AN: 152222 Hom.: 2477 Cov.: 33 AF XY: 0.165 AC XY: 12246 AN XY: 74428

African (AFR) AF: 0.0665 AC: 2765 AN: 41566

American (AMR) AF: 0.189 AC: 2896 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1041 AN: 5162

South Asian (SAS) AF: 0.198 AC: 955 AN: 4824

European-Finnish (FIN) AF: 0.165 AC: 1749 AN: 10604

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15107 AN: 67984

Other (OTH) AF: 0.153 AC: 323 AN: 2114

Alfa AF: 0.208 Hom.: 3590

Bravo AF: 0.164

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.62
PhyloP100		0.26
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: rs10504853; hg19: chr8-89089426;