12-55837247-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002429.6(MMP19):​c.1316G>A​(p.Arg439Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,614,212 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

MMP19
NM_002429.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.119
Variant links:
Genes affected
MMP19 (HGNC:7165): (matrix metallopeptidase 19) This gene encodes a member of a family of proteins that 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. The encoded protein is secreted as an inactive proprotein, which is activated upon cleavage by extracellular proteases. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Jan 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.00823167).
BS2
High AC in GnomAd4 at 29 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MMP19NM_002429.6 linkc.1316G>A p.Arg439Gln missense_variant Exon 9 of 9 ENST00000322569.9 NP_002420.1 Q99542-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MMP19ENST00000322569.9 linkc.1316G>A p.Arg439Gln missense_variant Exon 9 of 9 1 NM_002429.6 ENSP00000313437.4 Q99542-1

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00386
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000477
AC:
120
AN:
251470
Hom.:
0
AF XY:
0.000530
AC XY:
72
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00391
Gnomad SAS exome
AF:
0.00137
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000208
AC:
304
AN:
1461888
Hom.:
2
Cov.:
31
AF XY:
0.000243
AC XY:
177
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00302
Gnomad4 SAS exome
AF:
0.00145
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.0000234
Gnomad4 OTH exome
AF:
0.000414
GnomAD4 genome
AF:
0.000190
AC:
29
AN:
152324
Hom.:
0
Cov.:
32
AF XY:
0.000269
AC XY:
20
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00387
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000226
Hom.:
1
Bravo
AF:
0.000280
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000511
AC:
62
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

Familial cavitary optic disk anomaly Uncertain:1
Jun 08, 2020
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
14
DANN
Benign
0.92
DEOGEN2
Benign
0.047
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.045
N
LIST_S2
Benign
0.81
T;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.0082
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.50
N;.
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-0.60
N;N
REVEL
Benign
0.046
Sift
Benign
0.34
T;T
Sift4G
Benign
0.28
T;T
Polyphen
0.085
B;.
Vest4
0.055
MVP
0.15
MPC
0.12
ClinPred
0.0051
T
GERP RS
-2.5
Varity_R
0.037
gMVP
0.52

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: rs145643499; hg19: chr12-56231031; API