rs1711437

Variant names:

• chr11-102594495-C-T
• rs1711437
• NM_004771.4:c.1090+126G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004771.4(MMP20):​c.1090+126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,264,810 control chromosomes in the GnomAD database, including 127,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12307 hom., cov: 32)
  • Exomes 𝑓: 0.45 (114887 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0460
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-102594495-C-T is Benign according to our data. Variant chr11-102594495-C-T is described in ClinVar as Benign. ClinVar VariationId is 1241687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.1090+126G>A		intron_variant	Intron 7 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.1090+126G>A		intron_variant	Intron 7 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20	ENST00000544938.1	n.*193G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59885 AN: 151906 Hom.: 12295 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.450 AC: 500340 AN: 1112786 Hom.: 114887 AF XY: 0.455 AC XY: 255191 AN XY: 560568

African (AFR) AF: 0.284 AC: 7377 AN: 25984

American (AMR) AF: 0.433 AC: 15179 AN: 35022

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 10154 AN: 22976

East Asian (EAS) AF: 0.384 AC: 13262 AN: 34574

South Asian (SAS) AF: 0.570 AC: 41581 AN: 72950

European-Finnish (FIN) AF: 0.341 AC: 15129 AN: 44360

Middle Eastern (MID) AF: 0.495 AC: 1740 AN: 3518

European-Non Finnish (NFE) AF: 0.454 AC: 374605 AN: 825032

Other (OTH) AF: 0.441 AC: 21313 AN: 48370

GnomAD4 genome AF: 0.394 AC: 59913 AN: 152024 Hom.: 12307 Cov.: 32 AF XY: 0.391 AC XY: 29049 AN XY: 74294

African (AFR) AF: 0.293 AC: 12154 AN: 41456

American (AMR) AF: 0.420 AC: 6420 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1491 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1993 AN: 5170

South Asian (SAS) AF: 0.582 AC: 2802 AN: 4818

European-Finnish (FIN) AF: 0.317 AC: 3351 AN: 10560

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.445 AC: 30266 AN: 67944

Other (OTH) AF: 0.430 AC: 908 AN: 2112

Alfa AF: 0.442 Hom.: 8535

Bravo AF: 0.396

Asia WGS AF: 0.512 AC: 1782 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.5
DANN	Benign	0.79
PhyloP100		0.046
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1711437; hg19: chr11-102465226;