8-88056213-G-C

Variant names:

• chr8-88056213-G-C
• rs1186747588
• NM_005941.5:c.1288C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005941.5(MMP16):​c.1288C>G​(p.Leu430Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,448,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L430F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MMP16 NM_005941.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.66
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2879005).

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.1288C>G	p.Leu430Val	missense	Exon 8 of 10	NP_005932.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP16	ENST00000286614.11	TSL:1 MANE Select	c.1288C>G	p.Leu430Val	missense	Exon 8 of 10	ENSP00000286614.6	P51512-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 245068 AF XY: 0.00000754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448788 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 720866

African (AFR) AF: 0.00 AC: 0 AN: 33078

American (AMR) AF: 0.00 AC: 0 AN: 43230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25874

East Asian (EAS) AF: 0.00 AC: 0 AN: 39082

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104426

Other (OTH) AF: 0.00 AC: 0 AN: 59822

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.19
Sift	Uncertain	0.027	D
Sift4G	Benign	0.082	T
Polyphen		0.39	B
Vest4		0.36
MutPred		0.68		Gain of glycosylation at T429 (P = 0.0972)
MVP		0.55
MPC		1.2
ClinPred		0.52	D
GERP RS		5.9
Varity_R		0.11
gMVP		0.57
Mutation Taster		=83/17	polymorphism

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: rs1186747588; hg19: chr8-89068441;