11-102608687-T-C

Position:

• chr11-102608687-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP20	NM_004771.4	c.811+250A>G		intron_variant		ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.811+250A>G		intron_variant		1	NM_004771.4	ENSP00000260228.2
MMP20-AS1	ENST00000542119.1	n.86+1235T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.784

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.751

Alfa AF: 0.744 Hom.: 5325

Bravo AF: 0.745

Asia WGS AF: 0.885 AC: 3076 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.49

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: rs2509019; hg19: chr11-102479418;