chr11-102608925-TAATAATCTTACCGT-CTGG

Variant names:

• chr11-102608925-TAATAATCTTACCGT-CTGG
• rs1859555583
• NM_004771.4:c.809_811+12delACGGTAAGATTATTAinsCCAG

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_004771.4(MMP20):​c.809_811+12delACGGTAAGATTATTAinsCCAG​(p.Tyr270_Gly271delinsTer) variant causes a stop gained, splice donor, disruptive inframe deletion, splice region, synonymous, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Y270Y) has been classified as Benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MMP20 NM_004771.4 stop_gained, splice_donor, disruptive_inframe_deletion, splice_region, synonymous, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.24
• Publications: 1 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-AS1 (HGNC:56362): (MMP20 antisense RNA 1)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 11-102608925-TAATAATCTTACCGT-CTGG is Pathogenic according to our data. Variant chr11-102608925-TAATAATCTTACCGT-CTGG is described in ClinVar as [Pathogenic]. Clinvar id is 917993.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.809_811+12delACGGTAAGATTATTAinsCCAG	p.Tyr270_Gly271delinsTer	stop_gained, splice_donor_variant, disruptive_inframe_deletion, splice_region_variant, synonymous_variant, intron_variant	Exon 5 of 10	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.809_811+12delACGGTAAGATTATTAinsCCAG	p.Tyr270_Gly271delinsTer	stop_gained, splice_donor_variant, disruptive_inframe_deletion, splice_region_variant, synonymous_variant, intron_variant	Exon 5 of 10	1	NM_004771.4	ENSP00000260228.2
MMP20-AS1	ENST00000542119.2	n.233+1473_233+1487delTAATAATCTTACCGTinsCTGG		intron_variant	Intron 1 of 3	3
MMP20-AS1	ENST00000782665.1	n.233+1473_233+1487delTAATAATCTTACCGTinsCTGG		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Amelogenesis imperfecta hypomaturation type 2A2 Pathogenic:1

Jun 11, 2020

Leeds Amelogenesis Imperfecta Research Group, University of Leeds

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs1859555583; hg19: chr11-102479656;