NM_004771.4:c.812-1013A>C

Variant names:

• chr11-102607689-T-G
• rs1711423
• NM_004771.4:c.812-1013A>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.812-1013A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,004 control chromosomes in the GnomAD database, including 13,427 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 0.41 (13425 hom., cov: 31)
  • Exomes 𝑓: 0.44 (2 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• Publications: 6 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-AS1 (HGNC:56362): (MMP20 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 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.812-1013A>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.812-1013A>C		intron	N/A	ENSP00000260228.2	O60882
	MMP20-AS1	ENST00000542119.2	TSL:3	n.233+237T>G		intron	N/A
	MMP20-AS1	ENST00000544115.1	TSL:3	n.331-21T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62955 AN: 151870 Hom.: 13411 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.438 AC: 7 AN: 16 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

African (AFR) AF: 0.500 AC: 3 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 3 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.414 AC: 62996 AN: 151988 Hom.: 13425 Cov.: 31 AF XY: 0.412 AC XY: 30610 AN XY: 74316

African (AFR) AF: 0.332 AC: 13752 AN: 41450

American (AMR) AF: 0.445 AC: 6793 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1559 AN: 3466

East Asian (EAS) AF: 0.454 AC: 2340 AN: 5150

South Asian (SAS) AF: 0.585 AC: 2809 AN: 4804

European-Finnish (FIN) AF: 0.335 AC: 3542 AN: 10572

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30706 AN: 67960

Other (OTH) AF: 0.453 AC: 957 AN: 2112

Alfa AF: 0.416 Hom.: 1750

Bravo AF: 0.419

Asia WGS AF: 0.548 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-0.54
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: rs1711423; hg19: chr11-102478420;