rs141523340

Variant names:

• chr11-102578792-CAAAA-C
• rs141523340
• NM_004771.4:c.1351+243_1351+246delTTTT

Your query was ambiguous. Multiple possible variants found:

• chr11-102578792-CAAAA-C
• chr11-102578792-CAAAA-CAAAAAA
• chr11-102578792-CAAAA-CAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004771.4(MMP20):​c.1351+243_1351+246delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000293 in 136,462 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000029 (0 hom., cov: 25)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714
• Publications: 0 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 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta hypomaturation type 2A2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.1351+243_1351+246delTTTT		intron_variant	Intron 9 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.1351+243_1351+246delTTTT		intron_variant	Intron 9 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20	ENST00000542305.1	n.249+243_249+246delTTTT		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0000293 AC: 4 AN: 136462 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000155

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000317

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000293 AC: 4 AN: 136462 Hom.: 0 Cov.: 25 AF XY: 0.0000454 AC XY: 3 AN XY: 66080

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 36998

American (AMR) AF: 0.000155 AC: 2 AN: 12936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3282

East Asian (EAS) AF: 0.00 AC: 0 AN: 3960

South Asian (SAS) AF: 0.00 AC: 0 AN: 4320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.0000317 AC: 2 AN: 63150

Other (OTH) AF: 0.00 AC: 0 AN: 1894

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000022), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism

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: rs141523340; hg19: chr11-102449523;