chr12-131845986-G-T

Position:

• chr12-131845986-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.1204+537G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,018 control chromosomes in the GnomAD database, including 6,819 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 0.30 (6819 hom., cov: 32)
• Consequence: MMP17 NM_016155.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP17	NM_016155.7	c.1204+537G>T		intron_variant		ENST00000360564.5	NP_057239.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP17	ENST00000360564.5	c.1204+537G>T		intron_variant		1	NM_016155.7	ENSP00000353767	P1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44957 AN: 151900 Hom.: 6817 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.296 AC: 44995 AN: 152018 Hom.: 6819 Cov.: 32 AF XY: 0.293 AC XY: 21783 AN XY: 74310

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.312

Alfa AF: 0.209 Hom.: 602

Bravo AF: 0.299

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.54

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: rs10902456; hg19: chr12-132330531;