11-102578736-AAAAAAACAAAAAAC-A

Variant names:

• chr11-102578736-AAAAAAACAAAAAAC-A
• rs147058509
• NM_004771.4:c.1351+289_1351+302delGTTTTTTGTTTTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004771.4(MMP20):​c.1351+289_1351+302delGTTTTTTGTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (9455 hom., cov: 0)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.591
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 11-102578736-AAAAAAACAAAAAAC-A is Benign according to our data. Variant chr11-102578736-AAAAAAACAAAAAAC-A is described in ClinVar as [Benign]. Clinvar id is 1266612.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.1351+289_1351+302delGTTTTTTGTTTTTT		intron_variant	Intron 9 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.1351+289_1351+302delGTTTTTTGTTTTTT		intron_variant	Intron 9 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20	ENST00000542305.1	n.249+289_249+302delGTTTTTTGTTTTTT		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49095 AN: 150488 Hom.: 9454 Cov.: 0

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.326 AC: 49105 AN: 150606 Hom.: 9455 Cov.: 0 AF XY: 0.323 AC XY: 23756 AN XY: 73482

African (AFR) AF: 0.129 AC: 5277 AN: 40932

American (AMR) AF: 0.365 AC: 5514 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1547 AN: 3460

East Asian (EAS) AF: 0.110 AC: 557 AN: 5080

South Asian (SAS) AF: 0.422 AC: 2013 AN: 4774

European-Finnish (FIN) AF: 0.359 AC: 3675 AN: 10236

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.430 AC: 29138 AN: 67716

Other (OTH) AF: 0.367 AC: 768 AN: 2090

Alfa AF: 0.390 Hom.: 792

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147058509; hg19: chr11-102449467;