11-102613665-C-T

Variant names:

• chr11-102613665-C-T
• rs1784418
• NM_004771.4:c.375-1762G>A

Variant summary

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

The NM_004771.4(MMP20):​c.375-1762G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,928 control chromosomes in the GnomAD database, including 13,520 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 0.41 (13520 hom., cov: 32)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 31 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.375-1762G>A		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.375-1762G>A		intron_variant	Intron 2 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20-AS1	ENST00000542119.2	n.233+6213C>T		intron_variant	Intron 1 of 3	3
MMP20-AS1	ENST00000782665.1	n.234-3187C>T		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62923 AN: 151810 Hom.: 13503 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.414 AC: 62966 AN: 151928 Hom.: 13520 Cov.: 32 AF XY: 0.413 AC XY: 30671 AN XY: 74248

African (AFR) AF: 0.304 AC: 12599 AN: 41434

American (AMR) AF: 0.450 AC: 6864 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1605 AN: 3468

East Asian (EAS) AF: 0.459 AC: 2374 AN: 5170

South Asian (SAS) AF: 0.588 AC: 2822 AN: 4802

European-Finnish (FIN) AF: 0.371 AC: 3909 AN: 10534

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31301 AN: 67948

Other (OTH) AF: 0.454 AC: 956 AN: 2108

Alfa AF: 0.457 Hom.: 9024

Bravo AF: 0.415

Asia WGS AF: 0.551 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.67
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs1784418; hg19: chr11-102484396; COSMIC: COSV52774384;