11-102609690-G-A

Position:

• chr11-102609690-G-A

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.649+215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,176 control chromosomes in the GnomAD database, including 2,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2030 hom., cov: 32)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-102609690-G-A is Benign according to our data. Variant chr11-102609690-G-A is described in ClinVar as [Benign]. Clinvar id is 1296798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP20	NM_004771.4	c.649+215C>T		intron_variant		ENST00000260228.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP20	ENST00000260228.3	c.649+215C>T		intron_variant		1	NM_004771.4	P1
MMP20-AS1	ENST00000542119.1	n.86+2238G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22667 AN: 152058 Hom.: 2032 Cov.: 32

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.149 AC: 22659 AN: 152176 Hom.: 2030 Cov.: 32 AF XY: 0.151 AC XY: 11195 AN XY: 74382

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.141

Alfa AF: 0.180 Hom.: 3360

Bravo AF: 0.133

Asia WGS AF: 0.103 AC: 358 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	-0.90
CADD	Benign	0.038
DANN	Benign	0.54

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: rs10502005; hg19: chr11-102480421;