11-102625267-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004771.4(MMP20):c.53A>C(p.Lys18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,613,374 control chromosomes in the GnomAD database, including 347,848 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32181 hom., cov: 30)

Exomes 𝑓: 0.66 ( 315667 hom. )

Consequence

MMP20
NM_004771.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.99

Publications

48 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2664314E-6).

BP6

Variant 11-102625267-T-G is Benign according to our data. Variant chr11-102625267-T-G is described in ClinVar as Benign. ClinVar VariationId is 259539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4 link	c.53A>C	p.Lys18Thr	missense_variant	Exon 1 of 10	ENST00000260228.3	NP_004762.2	O60882

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP20	ENST00000260228.3 link	c.53A>C	p.Lys18Thr	missense_variant	Exon 1 of 10	1	NM_004771.4	ENSP00000260228.2	O60882
MMP20-AS1	ENST00000542119.2 link	n.234-1392T>G		intron_variant	Intron 1 of 3	3
MMP20-AS1	ENST00000782665.1 link	n.590-1392T>G		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98565

AN:

151816

Hom.:

32142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.625

Gnomad AMI

AF:

0.754

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.594

Gnomad EAS

AF:

0.830

Gnomad SAS

AF:

0.711

Gnomad FIN

AF:

0.653

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.658

GnomAD2 exomes

AF:

0.665

AC:

167017

AN:

251102

AF XY:

0.667

show subpopulations

Gnomad AFR exome

AF:

0.623

Gnomad AMR exome

AF:

0.670

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.833

Gnomad FIN exome

AF:

0.647

Gnomad NFE exome

AF:

0.643

Gnomad OTH exome

AF:

0.650

GnomAD4 exome

AF:

0.656

AC:

958554

AN:

1461438

Hom.:

315667

Cov.:

AF XY:

0.656

AC XY:

477161

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.621

AC:

20785

AN:

33474

American (AMR)

AF:

0.674

AC:

30150

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

15873

AN:

26126

East Asian (EAS)

AF:

0.842

AC:

33409

AN:

39686

South Asian (SAS)

AF:

0.695

AC:

59899

AN:

86244

European-Finnish (FIN)

AF:

0.642

AC:

34288

AN:

53378

Middle Eastern (MID)

AF:

0.688

AC:

3926

AN:

5706

European-Non Finnish (NFE)

AF:

0.648

AC:

720308

AN:

1111738

Other (OTH)

AF:

0.661

AC:

39916

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

18383

36767

55150

73534

91917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19058

38116

57174

76232

95290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.649

AC:

98662

AN:

151936

Hom.:

32181

Cov.:

AF XY:

0.653

AC XY:

48460

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.625

AC:

25899

AN:

41436

American (AMR)

AF:

0.673

AC:

10272

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.594

AC:

2059

AN:

3466

East Asian (EAS)

AF:

0.829

AC:

4286

AN:

5168

South Asian (SAS)

AF:

0.711

AC:

3420

AN:

4812

European-Finnish (FIN)

AF:

0.653

AC:

6871

AN:

10524

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.642

AC:

43590

AN:

67948

Other (OTH)

AF:

0.663

AC:

1400

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1737

3474

5211

6948

8685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.649

Hom.:

101567

Bravo

AF:

0.653

TwinsUK

AF:

0.653

AC:

2423

ALSPAC

AF:

0.645

AC:

2485

ESP6500AA

AF:

0.624

AC:

2751

ESP6500EA

AF:

0.644

AC:

5538

ExAC

AF:

0.662

AC:

80346

Asia WGS

AF:

0.795

AC:

2764

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Amelogenesis imperfecta hypomaturation type 2A2

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.035

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0000013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.0

PrimateAI

Benign

0.43

PROVEAN

Benign

0.46

REVEL

Benign

0.075

Sift

Benign

0.43

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.16

MPC

0.039

ClinPred

0.012

GERP RS

4.1

PromoterAI

0.070

Neutral

(source)

Varity_R

0.060

gMVP

0.47

Mutation Taster

=93/7

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over