11-102608691-C-CAAA

Variant names:

• chr11-102608691-C-CAAA
• rs5794187
• NM_004771.4:c.811+245_811+246insTTT

Variant summary

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

The NM_004771.4(MMP20):​c.811+245_811+246insTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,850 control chromosomes in the GnomAD database, including 13,309 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (13309 hom., cov: 33)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.254
• 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-AS1 (HGNC:56362): (MMP20 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-102608691-C-CAAA is Benign according to our data. Variant chr11-102608691-C-CAAA is described in ClinVar as [Benign]. Clinvar id is 1264163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.811+245_811+246insTTT		intron_variant	Intron 5 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.811+245_811+246insTTT		intron_variant	Intron 5 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20-AS1	ENST00000542119.2	n.233+1239_233+1240insAAA		intron_variant	Intron 1 of 3	3
MMP20-AS1	ENST00000782665.1	n.233+1239_233+1240insAAA		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62763 AN: 151732 Hom.: 13295 Cov.: 33

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.414 AC: 62804 AN: 151850 Hom.: 13309 Cov.: 33 AF XY: 0.411 AC XY: 30465 AN XY: 74190

African (AFR) AF: 0.331 AC: 13747 AN: 41474

American (AMR) AF: 0.444 AC: 6773 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1561 AN: 3470

East Asian (EAS) AF: 0.453 AC: 2340 AN: 5164

South Asian (SAS) AF: 0.584 AC: 2808 AN: 4806

European-Finnish (FIN) AF: 0.335 AC: 3530 AN: 10552

Middle Eastern (MID) AF: 0.497 AC: 144 AN: 290

European-Non Finnish (NFE) AF: 0.451 AC: 30557 AN: 67818

Other (OTH) AF: 0.453 AC: 956 AN: 2110

Alfa AF: 0.104 Hom.: 328

Asia WGS AF: 0.546 AC: 1902 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.25
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: rs5794187; hg19: chr11-102479422;