16-58026391-C-G

Variant names:

• chr16-58026391-C-G
• rs1490460561
• NM_002428.4:c.41C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002428.4(MMP15):​c.41C>G​(p.Thr14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,252,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: MMP15 NM_002428.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.190
• Publications: 0 publications found

Genes affected

MMP15 (HGNC:7161): (matrix metallopeptidase 15) This gene encodes a member of the peptidase M10 family and membrane-type subfamily of matrix metalloproteinases (MMPs). Proteins in this 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. Members of this subfamily contain a transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. The encoded preproprotein is proteolytically processed to generate the mature protease. This protein may play a role in cancer progression. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093009174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002428.4. 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
	MMP15	NM_002428.4	MANE Select	c.41C>G	p.Thr14Arg	missense	Exon 1 of 10	NP_002419.1	P51511

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP15	ENST00000219271.4	TSL:1 MANE Select	c.41C>G	p.Thr14Arg	missense	Exon 1 of 10	ENSP00000219271.3	P51511
	MMP15	ENST00000930621.1		c.41C>G	p.Thr14Arg	missense	Exon 1 of 11	ENSP00000600680.1
	MMP15	ENST00000907594.1		c.41C>G	p.Thr14Arg	missense	Exon 1 of 10	ENSP00000577653.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000471 AC: 59 AN: 1252264 Hom.: 0 Cov.: 30 AF XY: 0.0000457 AC XY: 28 AN XY: 613046

African (AFR) AF: 0.00 AC: 0 AN: 24648

American (AMR) AF: 0.00 AC: 0 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18582

East Asian (EAS) AF: 0.00 AC: 0 AN: 27872

South Asian (SAS) AF: 0.00 AC: 0 AN: 60074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3614

European-Non Finnish (NFE) AF: 0.0000579 AC: 59 AN: 1018354

Other (OTH) AF: 0.00 AC: 0 AN: 51514

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.19
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.046
Sift	Uncertain	0.010	D
Sift4G	Benign	0.061	T
Polyphen		0.040	B
Vest4		0.29
MutPred		0.25		Gain of methylation at T14 (P = 0.0297)
MVP		0.42
MPC		2.2
ClinPred		0.096	T
GERP RS		1.7
Varity_R		0.17
gMVP		0.47
Mutation Taster		=82/18	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: rs1490460561; hg19: chr16-58060295;