Variant 12-131838267-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_016155.7(MMP17):c.232C>A(p.Leu78Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,613,244 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 19 hom. )

Consequence

MMP17
NM_016155.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.18

Variant links:

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]

MMP17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016211122).

BP6

Variant 12-131838267-C-A is Benign according to our data. Variant chr12-131838267-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 782132.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP17	NM_016155.7 linkuse as main transcript	c.232C>A	p.Leu78Met	missense_variant	2/10	ENST00000360564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP17	ENST00000360564.5 linkuse as main transcript	c.232C>A	p.Leu78Met	missense_variant	2/10	1	NM_016155.7	P1	Q9ULZ9-1

Frequencies

GnomAD3 genomes

AF:

0.00279

AC:

425

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00392

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00289

AC:

721

AN:

249810

Hom.:

AF XY:

0.00332

AC XY:

450

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.000869

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00210

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00513

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.00382

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00437

AC:

6379

AN:

1460920

Hom.:

Cov.:

AF XY:

0.00444

AC XY:

3225

AN XY:

726760

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00519

Gnomad4 FIN exome

AF:

0.00108

Gnomad4 NFE exome

AF:

0.00493

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.00279

AC:

425

AN:

152324

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

215

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00392

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00375

Hom.:

Bravo

AF:

0.00259

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00283

AC:

344

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00355

EpiControl

AF:

0.00397

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

M_CAP

Benign

0.018

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.5

REVEL

Benign

0.26

Sift

Benign

0.27

Sift4G

Benign

0.064

Polyphen

1.0

Vest4

0.61

MVP

0.74

MPC

0.76

ClinPred

0.012

GERP RS

3.0

Varity_R

0.26

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over