11-102578919-T-A

Variant names:

• chr11-102578919-T-A
• rs7934921
• NM_004771.4:c.1351+120A>T

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.1351+120A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 748,500 control chromosomes in the GnomAD database, including 130,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30502 hom., cov: 32)
  • Exomes 𝑓: 0.57 (99753 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.418
• Publications: 7 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=-0.87).
• BP6: Variant 11-102578919-T-A is Benign according to our data. Variant chr11-102578919-T-A is described in ClinVar as [Benign]. Clinvar id is 1241072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.1351+120A>T		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+120A>T		intron_variant	Intron 9 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20	ENST00000542305.1	n.249+120A>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95186 AN: 151976 Hom.: 30459 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.596

GnomAD4 exome AF: 0.574 AC: 342132 AN: 596406 Hom.: 99753 AF XY: 0.566 AC XY: 182726 AN XY: 322978

African (AFR) AF: 0.756 AC: 12250 AN: 16198

American (AMR) AF: 0.583 AC: 20482 AN: 35146

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 10459 AN: 19902

East Asian (EAS) AF: 0.786 AC: 26382 AN: 33584

South Asian (SAS) AF: 0.484 AC: 31058 AN: 64124

European-Finnish (FIN) AF: 0.624 AC: 26170 AN: 41928

Middle Eastern (MID) AF: 0.571 AC: 2335 AN: 4086

European-Non Finnish (NFE) AF: 0.556 AC: 194453 AN: 349718

Other (OTH) AF: 0.585 AC: 18543 AN: 31720

GnomAD4 genome AF: 0.626 AC: 95280 AN: 152094 Hom.: 30502 Cov.: 32 AF XY: 0.629 AC XY: 46739 AN XY: 74362

African (AFR) AF: 0.757 AC: 31405 AN: 41506

American (AMR) AF: 0.601 AC: 9186 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1825 AN: 3470

East Asian (EAS) AF: 0.757 AC: 3913 AN: 5172

South Asian (SAS) AF: 0.495 AC: 2386 AN: 4824

European-Finnish (FIN) AF: 0.640 AC: 6764 AN: 10574

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37991 AN: 67948

Other (OTH) AF: 0.598 AC: 1265 AN: 2116

Alfa AF: 0.459 Hom.: 1205

Bravo AF: 0.632

Asia WGS AF: 0.635 AC: 2207 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.53
PhyloP100		-0.42
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: rs7934921; hg19: chr11-102449650; COSMIC: COSV107279678;