rs17174327

chr11-102607715-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004771.4(MMP20):c.812-1039G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,164 control chromosomes in the GnomAD database, including 751 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 0.088 (751 hom., cov: 32)
  • Exomes 𝑓: 0.094 (0 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP20	NM_004771.4	c.812-1039G>A		intron_variant		ENST00000260228.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP20	ENST00000260228.3	c.812-1039G>A		intron_variant		1	NM_004771.4	P1
MMP20-AS1	ENST00000542119.1	n.86+263C>T		intron_variant, non_coding_transcript_variant		3
MMP20-AS1	ENST00000544115.1	n.336C>T		non_coding_transcript_exon_variant	3/3	3
MMP20	ENST00000544938.1	n.136G>A		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13380 AN: 152014 Hom.: 751 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.0789

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0823

GnomAD4 exome AF: 0.0938 AC: 3 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 1 AN XY: 20

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0879 AC: 13376 AN: 152132 Hom.: 751 Cov.: 32 AF XY: 0.0869 AC XY: 6461 AN XY: 74356

Gnomad4 AFR AF: 0.0214

Gnomad4 AMR AF: 0.0725

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.0788

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.110 Hom.: 132

Bravo AF: 0.0799

Asia WGS AF: 0.0720 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.1
Dann	Benign	0.32

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: rs17174327; hg19: chr11-102478446;