12-131831679-G-C

Variant names:

• chr12-131831679-G-C
• rs4964926
• NM_016155.7:c.159+3026G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016155.7(MMP17):​c.159+3026G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 149,496 control chromosomes in the GnomAD database, including 55,896 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (55896 hom., cov: 22)
• Consequence: MMP17 NM_016155.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 4 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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.159+3026G>C		intron	N/A	NP_057239.4
	MMP17	NM_001411000.1		c.-94+1014G>C		intron	N/A	NP_001397929.1
	MMP17	NR_182296.1		n.261+3026G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP17	ENST00000360564.5	TSL:1 MANE Select	c.159+3026G>C		intron	N/A	ENSP00000353767.1
	MMP17	ENST00000535004.2	TSL:3	n.159+3026G>C		intron	N/A	ENSP00000445620.2
	MMP17	ENST00000545671.6	TSL:3	n.159+3026G>C		intron	N/A	ENSP00000444603.2

Frequencies

GnomAD3 genomes AF: 0.860 AC: 128520 AN: 149378 Hom.: 55866 Cov.: 22

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.867

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.860 AC: 128603 AN: 149496 Hom.: 55896 Cov.: 22 AF XY: 0.863 AC XY: 62862 AN XY: 72882

African (AFR) AF: 0.726 AC: 29288 AN: 40354

American (AMR) AF: 0.880 AC: 13185 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2789 AN: 3458

East Asian (EAS) AF: 0.999 AC: 4895 AN: 4900

South Asian (SAS) AF: 0.908 AC: 4197 AN: 4624

European-Finnish (FIN) AF: 0.940 AC: 9771 AN: 10390

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.914 AC: 61717 AN: 67530

Other (OTH) AF: 0.870 AC: 1795 AN: 2064

Alfa AF: 0.882 Hom.: 6965

Bravo AF: 0.850

Asia WGS AF: 0.936 AC: 3258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.34
PhyloP100		-3.0
Mutation Taster		=100/0	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: rs4964926; hg19: chr12-132316224;