rs767478911

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004771.4(MMP20):​c.1139G>T​(p.Arg380Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R380Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MMP20
NM_004771.4 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.15
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MMP20NM_004771.4 linkuse as main transcriptc.1139G>T p.Arg380Leu missense_variant 8/10 ENST00000260228.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MMP20ENST00000260228.3 linkuse as main transcriptc.1139G>T p.Arg380Leu missense_variant 8/101 NM_004771.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251376
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135848
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461840
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
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:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T
Eigen
Uncertain
0.30
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.038
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.9
M
MutationTaster
Benign
0.99
D
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-4.7
D
REVEL
Benign
0.17
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.035
D
Polyphen
1.0
D
Vest4
0.73
MutPred
0.63
Loss of disorder (P = 0.0965);
MVP
0.61
MPC
0.23
ClinPred
0.97
D
GERP RS
4.1
Varity_R
0.40
gMVP
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs767478911; hg19: chr11-102464278; API