rs1711423

Positions:

• chr11-102607689-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP20	NM_004771.4	c.812-1013A>C		intron_variant		ENST00000260228.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP20	ENST00000260228.3	c.812-1013A>C		intron_variant		1	NM_004771.4	P1
MMP20-AS1	ENST00000542119.1	n.86+237T>G		intron_variant, non_coding_transcript_variant		3
MMP20-AS1	ENST00000544115.1	n.331-21T>G		intron_variant, non_coding_transcript_variant		3
MMP20	ENST00000544938.1	n.155+7A>C		splice_region_variant, intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.375

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

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.453

Alfa AF: 0.420 Hom.: 1713

Bravo AF: 0.419

Asia WGS AF: 0.548 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs1711423; hg19: chr11-102478420;