11-102578792-C-CAA

Variant names:

• chr11-102578792-C-CAA
• rs141523340
• NM_004771.4:c.1351+245_1351+246dupTT

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+245_1351+246dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 136,508 control chromosomes in the GnomAD database, including 4,845 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (4845 hom., cov: 25)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75
• 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 11-102578792-C-CAA is Benign according to our data. Variant chr11-102578792-C-CAA is described in ClinVar as [Benign]. Clinvar id is 1289239.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.1351+245_1351+246dupTT		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+246_1351+247insTT		intron_variant	Intron 9 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20	ENST00000542305.1	n.249+246_249+247insTT		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 36433 AN: 136380 Hom.: 4838 Cov.: 25

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.267 AC: 36484 AN: 136508 Hom.: 4845 Cov.: 25 AF XY: 0.267 AC XY: 17657 AN XY: 66172

African (AFR) AF: 0.401 AC: 14890 AN: 37086

American (AMR) AF: 0.198 AC: 2568 AN: 12946

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 724 AN: 3280

East Asian (EAS) AF: 0.281 AC: 1110 AN: 3952

South Asian (SAS) AF: 0.152 AC: 657 AN: 4314

European-Finnish (FIN) AF: 0.243 AC: 2121 AN: 8732

Middle Eastern (MID) AF: 0.208 AC: 57 AN: 274

European-Non Finnish (NFE) AF: 0.217 AC: 13728 AN: 63128

Other (OTH) AF: 0.241 AC: 460 AN: 1912

Alfa AF: 0.0814 Hom.: 126

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		-1.7
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: rs141523340; hg19: chr11-102449523;