dbSNP rs1711420: MMP20:c.811+119A>G (chr11-102608818-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004771.4(MMP20):c.811+119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,069,792 control chromosomes in the GnomAD database, including 112,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 13439 hom., cov: 34)

Exomes 𝑓: 0.46 ( 99415 hom. )

Consequence

MMP20
NM_004771.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.36

Variant links:

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 links:

MMP20-AS1 (HGNC:56362): (MMP20 antisense RNA 1)

MMP20-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-102608818-T-C is Benign according to our data. Variant chr11-102608818-T-C is described in ClinVar as [Benign]. Clinvar id is 1221257.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4 link	c.811+119A>G		intron_variant	Intron 5 of 9	ENST00000260228.3	NP_004762.2	O60882

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3 link	c.811+119A>G		intron_variant	Intron 5 of 9	1	NM_004771.4	ENSP00000260228.2		O60882
MMP20-AS1	ENST00000542119.1 link	n.86+1366T>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

63045

AN:

152050

Hom.:

13425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.461

AC:

423464

AN:

917624

Hom.:

99415

AF XY:

0.467

AC XY:

223288

AN XY:

477978

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.467

Gnomad4 ASJ exome

AF:

0.462

Gnomad4 EAS exome

AF:

0.436

Gnomad4 SAS exome

AF:

0.575

Gnomad4 FIN exome

AF:

0.357

Gnomad4 NFE exome

AF:

0.462

Gnomad4 OTH exome

AF:

0.459

GnomAD4 genome

AF:

0.415

AC:

63086

AN:

152168

Hom.:

13439

Cov.:

AF XY:

0.412

AC XY:

30653

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.445

Gnomad4 ASJ

AF:

0.450

Gnomad4 EAS

AF:

0.454

Gnomad4 SAS

AF:

0.586

Gnomad4 FIN

AF:

0.336

Gnomad4 NFE

AF:

0.452

Gnomad4 OTH

AF:

0.454

Alfa

AF:

0.420

Hom.:

1712

Bravo

AF:

0.419

Asia WGS

AF:

0.546

AC:

1902

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.84

CADD

Benign

0.0060

DANN

Benign

0.30

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over