Genetic Variant NM_004771.4:c.812-1013A>C (chr11-102607689-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004771.4(MMP20):c.812-1013A>C 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 152,004 control chromosomes in the GnomAD database, including 13,427 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 ( 13425 hom., cov: 31)

Exomes 𝑓: 0.44 ( 2 hom. )

Consequence

MMP20
NM_004771.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.537

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4 link	c.812-1013A>C		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 link	c.812-1013A>C		intron_variant	Intron 5 of 9	1	NM_004771.4	ENSP00000260228.2

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

62955

AN:

151870

Hom.:

13411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.584

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.446

GnomAD4 exome

AF:

0.438

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.414

AC:

62996

AN:

151988

Hom.:

13425

Cov.:

AF XY:

0.412

AC XY:

30610

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.332

AC:

13752

AN:

41450

American (AMR)

AF:

0.445

AC:

6793

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

1559

AN:

3466

East Asian (EAS)

AF:

0.454

AC:

2340

AN:

5150

South Asian (SAS)

AF:

0.585

AC:

2809

AN:

4804

European-Finnish (FIN)

AF:

0.335

AC:

3542

AN:

10572

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.452

AC:

30706

AN:

67960

Other (OTH)

AF:

0.453

AC:

957

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1877

3753

5630

7506

9383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.416

Hom.:

1750

Bravo

AF:

0.419

Asia WGS

AF:

0.548

AC:

1906

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.1

(source)

DANN

Benign

0.40

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over