12-131851047-G-A

Variant names:

• chr12-131851047-G-A
• rs11835665
• NM_016155.7:c.1585G>A

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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: 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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016155.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP17	NM_016155.7	MANE Select	c.1585G>A	p.Asp529Asn	missense	Exon 10 of 10	NP_057239.4
	MMP17	NM_001411000.1		c.1333G>A	p.Asp445Asn	missense	Exon 10 of 10	NP_001397929.1
	MMP17	NR_182296.1		n.1869G>A		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP17	ENST00000360564.5	TSL:1 MANE Select	c.1585G>A	p.Asp529Asn	missense	Exon 10 of 10	ENSP00000353767.1
	MMP17	ENST00000535291.5	TSL:1	c.1333G>A	p.Asp445Asn	missense	Exon 9 of 9	ENSP00000441106.1
	MMP17	ENST00000535004.2	TSL:3	n.*218G>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000445620.2

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

GnomAD2 exomes AF: 0.183 AC: 43923 AN: 240422 AF XY: 0.184

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 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

African (AFR) AF: 0.177 AC: 5906 AN: 33280

American (AMR) AF: 0.168 AC: 7407 AN: 44118

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 5084 AN: 25896

East Asian (EAS) AF: 0.000686 AC: 27 AN: 39380

South Asian (SAS) AF: 0.142 AC: 12185 AN: 85614

European-Finnish (FIN) AF: 0.239 AC: 12431 AN: 52058

Middle Eastern (MID) AF: 0.175 AC: 1002 AN: 5742

European-Non Finnish (NFE) AF: 0.221 AC: 245581 AN: 1109550

Other (OTH) AF: 0.201 AC: 12081 AN: 60068

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

African (AFR) AF: 0.182 AC: 7565 AN: 41542

American (AMR) AF: 0.199 AC: 3046 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.127 AC: 611 AN: 4830

European-Finnish (FIN) AF: 0.232 AC: 2462 AN: 10596

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14873 AN: 67982

Other (OTH) AF: 0.209 AC: 441 AN: 2114

Alfa AF: 0.197 Hom.: 5610

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 v4.9

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
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.073
Sift	Benign	0.045	D
Sift4G	Benign	0.11	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
Mutation Taster		=95/5	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: rs11835665; hg19: chr12-132335592; COSMIC: COSV107473500; COSMIC: COSV107473500;