rs577048107

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005941.5(MMP16):​c.1772G>T​(p.Gly591Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,088 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 6.8e-7 ( 0 hom. )

Consequence

MMP16
NM_005941.5 missense

Scores

4
11
4

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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MMP16NM_005941.5 linkc.1772G>T p.Gly591Val missense_variant Exon 10 of 10 ENST00000286614.11 NP_005932.2 P51512-1
MMP16XM_024447154.2 linkc.983G>T p.Gly328Val 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>T p.Gly591Val missense_variant Exon 10 of 10 1 NM_005941.5 ENSP00000286614.6 P51512-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460088
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726158
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000386
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.052
D
MetaRNN
Uncertain
0.47
T
MetaSVM
Benign
-0.52
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-5.6
D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.98
D
Vest4
0.55
MutPred
0.44
Loss of disorder (P = 0.0724);
MVP
0.44
MPC
2.1
ClinPred
0.98
D
GERP RS
5.6
Varity_R
0.84
gMVP
0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-89053741; COSMIC: COSV54149863; API