8-88041513-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005941.5(MMP16):​c.1772G>A​(p.Gly591Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G591A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MMP16
NM_005941.5 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.82
Variant links:
Genes affected
MMP16 (HGNC:7162): (matrix metallopeptidase 16) Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The encoded protein activates MMP2 by cleavage. This gene was once referred to as MT-MMP2, but was renamed as MT-MMP3 or MMP16. [provided by RefSeq, Oct 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31141508).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MMP16NM_005941.5 linkc.1772G>A p.Gly591Glu missense_variant Exon 10 of 10 ENST00000286614.11 NP_005932.2 P51512-1
MMP16XM_024447154.2 linkc.983G>A p.Gly328Glu missense_variant Exon 7 of 7 XP_024302922.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MMP16ENST00000286614.11 linkc.1772G>A p.Gly591Glu missense_variant Exon 10 of 10 1 NM_005941.5 ENSP00000286614.6 P51512-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248302
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134002
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000467
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000137
AC:
2
AN:
1460058
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726138
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000906
AC:
11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
1.7
L
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-4.4
D
REVEL
Benign
0.21
Sift
Benign
0.084
T
Sift4G
Benign
0.20
T
Polyphen
0.35
B
Vest4
0.54
MVP
0.31
MPC
2.1
ClinPred
0.92
D
GERP RS
5.6
Varity_R
0.37
gMVP
0.83

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

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

Other links and lift over

dbSNP: rs577048107; hg19: chr8-89053741; API