8-88116526-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005941.5(MMP16):​c.1064G>A​(p.Arg355His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

MMP16
NM_005941.5 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.05
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 Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MMP16NM_005941.5 linkc.1064G>A p.Arg355His missense_variant Exon 6 of 10 ENST00000286614.11 NP_005932.2 P51512-1
MMP16XM_024447154.2 linkc.275G>A p.Arg92His missense_variant Exon 3 of 7 XP_024302922.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MMP16ENST00000286614.11 linkc.1064G>A p.Arg355His missense_variant Exon 6 of 10 1 NM_005941.5 ENSP00000286614.6 P51512-1
MMP16ENST00000544227.5 linkn.1064G>A non_coding_transcript_exon_variant Exon 6 of 8 1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151746
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461348
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
726974
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151746
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74036
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1064G>A (p.R355H) alteration is located in exon 6 (coding exon 6) of the MMP16 gene. This alteration results from a G to A substitution at nucleotide position 1064, causing the arginine (R) at amino acid position 355 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.15
T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.45
T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.16
Sift
Uncertain
0.012
D
Sift4G
Uncertain
0.0090
D
Polyphen
0.98
D
Vest4
0.39
MutPred
0.66
Loss of MoRF binding (P = 0.0275);
MVP
0.49
MPC
2.0
ClinPred
0.93
D
GERP RS
5.0
Varity_R
0.14
gMVP
0.56

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: rs1013166264; hg19: chr8-89128755; API