NM_004771.4:c.954-4768T>C

Variant names:

• chr11-102599525-A-G
• rs10895322
• NM_004771.4:c.954-4768T>C

Variant summary

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

The NM_004771.4(MMP20):​c.954-4768T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0963 in 152,308 control chromosomes in the GnomAD database, including 895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.096 (895 hom., cov: 32)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.60
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP20	NM_004771.4	MANE Select	c.954-4768T>C		intron	N/A	NP_004762.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP20	ENST00000260228.3	TSL:1 MANE Select	c.954-4768T>C		intron	N/A	ENSP00000260228.2	O60882
	MMP20	ENST00000544938.1	TSL:3	n.593-4768T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14650 AN: 152190 Hom.: 892 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0963 AC: 14662 AN: 152308 Hom.: 895 Cov.: 32 AF XY: 0.101 AC XY: 7559 AN XY: 74474

African (AFR) AF: 0.0744 AC: 3094 AN: 41566

American (AMR) AF: 0.150 AC: 2288 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1499 AN: 5190

South Asian (SAS) AF: 0.0598 AC: 289 AN: 4832

European-Finnish (FIN) AF: 0.133 AC: 1414 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0802 AC: 5456 AN: 68020

Other (OTH) AF: 0.0908 AC: 192 AN: 2114

Alfa AF: 0.0801 Hom.: 871

Bravo AF: 0.0973

Asia WGS AF: 0.149 AC: 515 AN: 3478

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.092
DANN	Benign	0.51
PhyloP100		-1.6
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: rs10895322; hg19: chr11-102470256;