chr11-102590046-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004771.4(MMP20):​c.1247+3393C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,892 control chromosomes in the GnomAD database, including 20,232 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 20232 hom., cov: 31)

Consequence

MMP20
NM_004771.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

8 publications found
Variant links:
Genes affected
MMP20 (HGNC:7167): (matrix metallopeptidase 20) 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 protein encoded by this gene degrades amelogenin, the major protein component of dental enamel matrix, and thus thought to play a role in tooth enamel formation. A mutation in this gene, which alters the normal splice pattern and results in premature termination of the encoded protein, has been associated with amelogenesis imperfecta. This gene is part of a cluster of MMP genes located on chromosome 11q22.3. [provided by RefSeq, Aug 2011]
MMP20 Gene-Disease associations (from GenCC):
  • amelogenesis imperfecta hypomaturation type 2A2
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • amelogenesis imperfecta type 2
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MMP20NM_004771.4 linkc.1247+3393C>A intron_variant Intron 8 of 9 ENST00000260228.3 NP_004762.2 O60882

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MMP20ENST00000260228.3 linkc.1247+3393C>A intron_variant Intron 8 of 9 1 NM_004771.4 ENSP00000260228.2 O60882

Frequencies

GnomAD3 genomes
AF:
0.509
AC:
77191
AN:
151774
Hom.:
20221
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.394
Gnomad AMI
AF:
0.507
Gnomad AMR
AF:
0.506
Gnomad ASJ
AF:
0.522
Gnomad EAS
AF:
0.533
Gnomad SAS
AF:
0.673
Gnomad FIN
AF:
0.510
Gnomad MID
AF:
0.595
Gnomad NFE
AF:
0.563
Gnomad OTH
AF:
0.525
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.508
AC:
77218
AN:
151892
Hom.:
20232
Cov.:
31
AF XY:
0.508
AC XY:
37676
AN XY:
74238
show subpopulations
African (AFR)
AF:
0.394
AC:
16305
AN:
41406
American (AMR)
AF:
0.505
AC:
7715
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.522
AC:
1813
AN:
3470
East Asian (EAS)
AF:
0.533
AC:
2746
AN:
5154
South Asian (SAS)
AF:
0.673
AC:
3236
AN:
4810
European-Finnish (FIN)
AF:
0.510
AC:
5374
AN:
10530
Middle Eastern (MID)
AF:
0.595
AC:
175
AN:
294
European-Non Finnish (NFE)
AF:
0.563
AC:
38274
AN:
67940
Other (OTH)
AF:
0.531
AC:
1119
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1887
3774
5661
7548
9435
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
696
1392
2088
2784
3480
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.552
Hom.:
88532
Bravo
AF:
0.504
Asia WGS
AF:
0.619
AC:
2155
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.2
DANN
Benign
0.70
PhyloP100
-0.098
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1711399; hg19: chr11-102460777; API