rs10895322

chr11-102599525-A-G

Variant summary

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

The NM_004771.4(MMP20):c.954-4768T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0963 in 152,308 control chromosomes in the GnomAD database, including 895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.096 (895 hom., cov: 32)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.60

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP20	NM_004771.4	c.954-4768T>C		intron_variant		ENST00000260228.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP20	ENST00000260228.3	c.954-4768T>C		intron_variant		1	NM_004771.4	P1
MMP20	ENST00000544938.1	n.593-4768T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14650 AN: 152190 Hom.: 892 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0963 AC: 14662 AN: 152308 Hom.: 895 Cov.: 32 AF XY: 0.101 AC XY: 7559 AN XY: 74474

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.0598

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.0802

Gnomad4 OTH AF: 0.0908

Alfa AF: 0.0799 Hom.: 691

Bravo AF: 0.0973

Asia WGS AF: 0.149 AC: 515 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

not provided

Department of Ophthalmology and Visual Sciences Kyoto University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.092
Dann	Benign	0.51

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: rs10895322; hg19: chr11-102470256;