11-102614822-G-A

Variant names:

• chr11-102614822-G-A
• rs7126560
• NM_004771.4:c.374+1990C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004771.4(MMP20):​c.374+1990C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,482 control chromosomes in the GnomAD database, including 1,413 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1413 hom., cov: 32)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.374+1990C>T		intron_variant	Intron 2 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.374+1990C>T		intron_variant	Intron 2 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20-AS1	ENST00000542119.2	n.233+7370G>A		intron_variant	Intron 1 of 3	3
MMP20-AS1	ENST00000782665.1	n.234-2030G>A		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19441 AN: 151368 Hom.: 1409 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.128 AC: 19462 AN: 151482 Hom.: 1413 Cov.: 32 AF XY: 0.132 AC XY: 9774 AN XY: 73982

African (AFR) AF: 0.122 AC: 5025 AN: 41294

American (AMR) AF: 0.164 AC: 2494 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1770 AN: 5162

South Asian (SAS) AF: 0.0842 AC: 405 AN: 4812

European-Finnish (FIN) AF: 0.143 AC: 1477 AN: 10326

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7514 AN: 67884

Other (OTH) AF: 0.117 AC: 246 AN: 2098

Alfa AF: 0.119 Hom.: 149

Bravo AF: 0.133

Asia WGS AF: 0.203 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.5
DANN	Benign	0.63
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7126560; hg19: chr11-102485553;