NM_004771.4:c.1248-3123T>G

Variant names:

• chr11-102582265-A-C
• rs1784410
• NM_004771.4:c.1248-3123T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004771.4(MMP20):​c.1248-3123T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,910 control chromosomes in the GnomAD database, including 20,910 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 0.52 (20910 hom., cov: 31)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP20	NM_004771.4	MANE Select	c.1248-3123T>G		intron	N/A	NP_004762.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP20	ENST00000260228.3	TSL:1 MANE Select	c.1248-3123T>G		intron	N/A	ENSP00000260228.2
	MMP20	ENST00000542305.1	TSL:2	n.145+1198T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78897 AN: 151792 Hom.: 20896 Cov.: 31

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.520 AC: 78935 AN: 151910 Hom.: 20910 Cov.: 31 AF XY: 0.518 AC XY: 38429 AN XY: 74236

African (AFR) AF: 0.453 AC: 18751 AN: 41406

American (AMR) AF: 0.514 AC: 7841 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1796 AN: 3466

East Asian (EAS) AF: 0.392 AC: 2026 AN: 5166

South Asian (SAS) AF: 0.661 AC: 3176 AN: 4806

European-Finnish (FIN) AF: 0.508 AC: 5353 AN: 10538

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38213 AN: 67956

Other (OTH) AF: 0.543 AC: 1144 AN: 2106

Alfa AF: 0.543 Hom.: 10547

Bravo AF: 0.518

Asia WGS AF: 0.565 AC: 1965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		-0.097
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: rs1784410; hg19: chr11-102452996;