NM_004771.4:c.811+113A>G

Variant names:

• chr11-102608824-T-C
• rs1711419
• NM_004771.4:c.811+113A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004771.4(MMP20):​c.811+113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 1,132,582 control chromosomes in the GnomAD database, including 338,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45496 hom., cov: 34)
  • Exomes 𝑓: 0.77 (292566 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.494
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-102608824-T-C is Benign according to our data. Variant chr11-102608824-T-C is described in ClinVar as [Benign]. Clinvar id is 1238048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.811+113A>G		intron_variant	Intron 5 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.811+113A>G		intron_variant	Intron 5 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20-AS1	ENST00000542119.2	n.233+1372T>C		intron_variant	Intron 1 of 3	3
MMP20-AS1	ENST00000782665.1	n.233+1372T>C		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117396 AN: 152106 Hom.: 45461 Cov.: 34

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 0.771 AC: 756202 AN: 980358 Hom.: 292566 AF XY: 0.771 AC XY: 391429 AN XY: 507516

African (AFR) AF: 0.770 AC: 18358 AN: 23846

American (AMR) AF: 0.751 AC: 32626 AN: 43434

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 15992 AN: 23142

East Asian (EAS) AF: 0.968 AC: 36122 AN: 37320

South Asian (SAS) AF: 0.779 AC: 58682 AN: 75284

European-Finnish (FIN) AF: 0.781 AC: 39468 AN: 50530

Middle Eastern (MID) AF: 0.728 AC: 2357 AN: 3236

European-Non Finnish (NFE) AF: 0.763 AC: 518050 AN: 678804

Other (OTH) AF: 0.772 AC: 34547 AN: 44762

GnomAD4 genome AF: 0.772 AC: 117484 AN: 152224 Hom.: 45496 Cov.: 34 AF XY: 0.773 AC XY: 57545 AN XY: 74430

African (AFR) AF: 0.769 AC: 31928 AN: 41536

American (AMR) AF: 0.758 AC: 11605 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2383 AN: 3470

East Asian (EAS) AF: 0.978 AC: 5068 AN: 5182

South Asian (SAS) AF: 0.797 AC: 3840 AN: 4818

European-Finnish (FIN) AF: 0.785 AC: 8310 AN: 10588

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51737 AN: 68012

Other (OTH) AF: 0.768 AC: 1621 AN: 2110

Alfa AF: 0.759 Hom.: 6155

Bravo AF: 0.774

Asia WGS AF: 0.891 AC: 3100 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.43
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: rs1711419; hg19: chr11-102479555;