chr11-102590046-G-T

Variant names:

• chr11-102590046-G-T
• rs1711399
• NM_004771.4:c.1247+3393C>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.1247+3393C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,892 control chromosomes in the GnomAD database, including 20,232 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 0.51 (20232 hom., cov: 31)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.1247+3393C>A		intron_variant	Intron 8 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.1247+3393C>A		intron_variant	Intron 8 of 9	1	NM_004771.4	ENSP00000260228.2

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77191 AN: 151774 Hom.: 20221 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.508 AC: 77218 AN: 151892 Hom.: 20232 Cov.: 31 AF XY: 0.508 AC XY: 37676 AN XY: 74238

African (AFR) AF: 0.394 AC: 16305 AN: 41406

American (AMR) AF: 0.505 AC: 7715 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1813 AN: 3470

East Asian (EAS) AF: 0.533 AC: 2746 AN: 5154

South Asian (SAS) AF: 0.673 AC: 3236 AN: 4810

European-Finnish (FIN) AF: 0.510 AC: 5374 AN: 10530

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38274 AN: 67940

Other (OTH) AF: 0.531 AC: 1119 AN: 2108

Alfa AF: 0.552 Hom.: 88532

Bravo AF: 0.504

Asia WGS AF: 0.619 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		-0.098
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: rs1711399; hg19: chr11-102460777;