NM_004771.4:c.*484T>C

Variant names:

• chr11-102576842-A-G
• rs531522695
• NM_004771.4:c.*484T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_004771.4(MMP20):​c.*484T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 171,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: MMP20 NM_004771.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.510
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000657 (10/152320) while in subpopulation SAS AF = 0.00207 (10/4826). AF 95% confidence interval is 0.00112. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.*484T>C		3_prime_UTR	Exon 10 of 10	NP_004762.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP20	ENST00000260228.3	TSL:1 MANE Select	c.*484T>C		3_prime_UTR	Exon 10 of 10	ENSP00000260228.2	O60882

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000409 AC: 8 AN: 19562 Hom.: 0 Cov.: 0 AF XY: 0.000650 AC XY: 7 AN XY: 10762

African (AFR) AF: 0.00 AC: 0 AN: 94

American (AMR) AF: 0.00 AC: 0 AN: 2616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 252

East Asian (EAS) AF: 0.00 AC: 0 AN: 998

South Asian (SAS) AF: 0.00291 AC: 8 AN: 2746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 36

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 11488

Other (OTH) AF: 0.00 AC: 0 AN: 828

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6 AN XY: 74490

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

Asia WGS AF: 0.00202 AC: 7 AN: 3474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Amelogenesis imperfecta hypomaturation type 2A2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.65
DANN	Benign	0.62
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism

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: rs531522695; hg19: chr11-102447573;