rs2509019

Variant names:

• chr11-102608687-T-C
• rs2509019
• NM_004771.4:c.811+250A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004771.4(MMP20):​c.811+250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,882 control chromosomes in the GnomAD database, including 42,533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.75 (42533 hom., cov: 33)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69
• 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-AS1 (HGNC:56362): (MMP20 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 11-102608687-T-C is Benign according to our data. Variant chr11-102608687-T-C is described in ClinVar as Benign. ClinVar VariationId is 1228002.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 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.811+250A>G		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.811+250A>G		intron	N/A	ENSP00000260228.2	O60882
	MMP20-AS1	ENST00000542119.2	TSL:3	n.233+1235T>C		intron	N/A
	MMP20-AS1	ENST00000782665.1		n.233+1235T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113284 AN: 151764 Hom.: 42506 Cov.: 33

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.667

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.748

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.746 AC: 113357 AN: 151882 Hom.: 42533 Cov.: 33 AF XY: 0.748 AC XY: 55497 AN XY: 74214

African (AFR) AF: 0.683 AC: 28289 AN: 41440

American (AMR) AF: 0.744 AC: 11373 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2383 AN: 3470

East Asian (EAS) AF: 0.978 AC: 5062 AN: 5176

South Asian (SAS) AF: 0.796 AC: 3832 AN: 4812

European-Finnish (FIN) AF: 0.784 AC: 8277 AN: 10556

Middle Eastern (MID) AF: 0.662 AC: 192 AN: 290

European-Non Finnish (NFE) AF: 0.760 AC: 51568 AN: 67832

Other (OTH) AF: 0.751 AC: 1588 AN: 2114

Alfa AF: 0.757 Hom.: 56775

Bravo AF: 0.745

Asia WGS AF: 0.885 AC: 3076 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		-1.7
Mutation Taster		=7/93	disease causing

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: rs2509019; hg19: chr11-102479418;