NM_016155.7:c.1585G>C

Variant names:

• chr12-131851047-G-C
• NM_016155.7:c.1585G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016155.7(MMP17):​c.1585G>C​(p.Asp529His) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MMP17 NM_016155.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65

Genes affected

MMP17 (HGNC:7163): (matrix metallopeptidase 17) 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 is unique among the membrane-type matrix metalloproteinases in that it is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. Elevated expression of the encoded protein has been observed in osteoarthritis and multiple human cancers. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21463785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP17	NM_016155.7	c.1585G>C	p.Asp529His	missense_variant	Exon 10 of 10	ENST00000360564.5	NP_057239.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP17	ENST00000360564.5	c.1585G>C	p.Asp529His	missense_variant	Exon 10 of 10	1	NM_016155.7	ENSP00000353767.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456008 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 724198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T;.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.55	T;T;T
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.98	D;.;.
Vest4		0.21
MutPred		0.40		Gain of catalytic residue at S531 (P = 0.0021);.;.;
MVP		0.44
MPC		0.72
ClinPred		0.71	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.17
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-132335592;