12-131831679-G-C

Position:

• chr12-131831679-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP17	NM_016155.7	c.159+3026G>C		intron_variant		ENST00000360564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP17	ENST00000360564.5	c.159+3026G>C		intron_variant		1	NM_016155.7	P1
MMP17	ENST00000535004.2	c.159+3026G>C		intron_variant, NMD_transcript_variant		3
MMP17	ENST00000545671.6	c.159+3026G>C		intron_variant, NMD_transcript_variant		3
MMP17	ENST00000545790.6	c.159+3026G>C		intron_variant, NMD_transcript_variant		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

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.908

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.914

Gnomad4 OTH AF: 0.870

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.34

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: rs4964926; hg19: chr12-132316224;