11-102598550-C-T

Variant names:

• chr11-102598550-C-T
• rs1711433
• NM_004771.4:c.954-3793G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004771.4(MMP20):​c.954-3793G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,206 control chromosomes in the GnomAD database, including 57,137 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 0.87 (57137 hom., cov: 32)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 8 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.954-3793G>A		intron_variant	Intron 6 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.954-3793G>A		intron_variant	Intron 6 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20	ENST00000544938.1	n.593-3793G>A		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131624 AN: 152088 Hom.: 57124 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.870

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.865 AC: 131680 AN: 152206 Hom.: 57137 Cov.: 32 AF XY: 0.867 AC XY: 64517 AN XY: 74430

African (AFR) AF: 0.799 AC: 33178 AN: 41500

American (AMR) AF: 0.863 AC: 13204 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3083 AN: 3466

East Asian (EAS) AF: 0.992 AC: 5141 AN: 5182

South Asian (SAS) AF: 0.849 AC: 4101 AN: 4828

European-Finnish (FIN) AF: 0.928 AC: 9834 AN: 10600

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60211 AN: 68016

Other (OTH) AF: 0.871 AC: 1843 AN: 2116

Alfa AF: 0.878 Hom.: 111165

Bravo AF: 0.859

Asia WGS AF: 0.916 AC: 3185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.38
PhyloP100		-1.5
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

Other links and lift over

dbSNP: rs1711433; hg19: chr11-102469281;