rs11835665

chr12-131851047-G-Achr12-131851047-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016155.7(MMP17):c.1585G>A(p.Asp529Asn) variant causes a missense change. The variant allele was found at a frequency of 0.206 in 1,607,916 control chromosomes in the GnomAD database, including 35,848 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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: 𝑓 0.20 (3085 hom., cov: 33)
  • Exomes 𝑓: 0.21 (32763 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043974817).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP17	NM_016155.7	c.1585G>A	p.Asp529Asn	missense_variant	10/10	ENST00000360564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP17	ENST00000360564.5	c.1585G>A	p.Asp529Asn	missense_variant	10/10	1	NM_016155.7	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29829 AN: 152092 Hom.: 3078 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.208

GnomAD3 exomes AF: 0.183 AC: 43923 AN: 240422 Hom.: 4440 AF XY: 0.184 AC XY: 24086 AN XY: 131088

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.166

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.000950

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.207 AC: 301704 AN: 1455706 Hom.: 32763 Cov.: 34 AF XY: 0.205 AC XY: 148781 AN XY: 724026

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.000686

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.196 AC: 29863 AN: 152210 Hom.: 3085 Cov.: 33 AF XY: 0.195 AC XY: 14532 AN XY: 74412

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.209

Alfa AF: 0.194 Hom.: 3767

Bravo AF: 0.191

TwinsUK AF: 0.226 AC: 838

ALSPAC AF: 0.212 AC: 818

ESP6500AA AF: 0.180 AC: 791

ESP6500EA AF: 0.216 AC: 1858

ExAC AF: 0.182 AC: 21978

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	16
Dann	Uncertain	0.99
DEOGEN2	Benign	0.16	T;.;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.61	T;T;T
MetaRNN	Benign	0.0044	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	L;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.073
Sift	Benign	0.045	D;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.040	B;.;.
Vest4		0.094
MPC		0.20
ClinPred		0.0088	T
GERP RS		1.5
Varity_R		0.094
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs11835665; hg19: chr12-132335592;