rs2292730

Positions:

• chr11-102577525-A-G
• chr11-102577525-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004771.4(MMP20):​c.1352-99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 843,940 control chromosomes in the GnomAD database, including 144,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30524 hom., cov: 33)
  • Exomes 𝑓: 0.57 (113711 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.50

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-102577525-A-G is Benign according to our data. Variant chr11-102577525-A-G is described in ClinVar as [Benign]. Clinvar id is 1262923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP20	NM_004771.4	c.1352-99T>C		intron_variant		ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.1352-99T>C		intron_variant		1	NM_004771.4	ENSP00000260228.2
MMP20	ENST00000542305.1	n.250-99T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95237 AN: 152002 Hom.: 30481 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.568 AC: 392617 AN: 691820 Hom.: 113711 AF XY: 0.561 AC XY: 205754 AN XY: 366540

Gnomad4 AFR exome AF: 0.756

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.535

Gnomad4 EAS exome AF: 0.786

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.549

Gnomad4 OTH exome AF: 0.582

GnomAD4 genome AF: 0.627 AC: 95331 AN: 152120 Hom.: 30524 Cov.: 33 AF XY: 0.629 AC XY: 46751 AN XY: 74358

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.600

Alfa AF: 0.559 Hom.: 47085

Bravo AF: 0.632

Asia WGS AF: 0.633 AC: 2200 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.64
DANN	Benign	0.48

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: rs2292730; hg19: chr11-102448256; COSMIC: COSV52774928;