11-102578780-A-AAC

Variant names:

• chr11-102578780-A-AAC
• rs10670953
• NM_004771.4:c.1351+257_1351+258dupGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004771.4(MMP20):​c.1351+257_1351+258dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (6745 hom., cov: 0)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-102578780-A-AAC is Benign according to our data. Variant chr11-102578780-A-AAC is described in ClinVar as [Benign]. Clinvar id is 1278244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.1351+257_1351+258dupGT		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+258_1351+259insGT		intron_variant	Intron 9 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20	ENST00000542305.1	n.249+258_249+259insGT		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 44504 AN: 136944 Hom.: 6742 Cov.: 0

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.325 AC: 44524 AN: 137028 Hom.: 6745 Cov.: 0 AF XY: 0.328 AC XY: 21972 AN XY: 66908

African (AFR) AF: 0.382 AC: 12990 AN: 34048

American (AMR) AF: 0.322 AC: 4539 AN: 14086

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 970 AN: 3270

East Asian (EAS) AF: 0.334 AC: 1523 AN: 4560

South Asian (SAS) AF: 0.174 AC: 766 AN: 4402

European-Finnish (FIN) AF: 0.402 AC: 3931 AN: 9776

Middle Eastern (MID) AF: 0.296 AC: 81 AN: 274

European-Non Finnish (NFE) AF: 0.297 AC: 18950 AN: 63836

Other (OTH) AF: 0.308 AC: 591 AN: 1916

Alfa AF: 0.105 Hom.: 186

Asia WGS AF: 0.238 AC: 825 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10670953; hg19: chr11-102449511;