chr11-102625267-T-G

Position:

chr11-102625267-T-G

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 made for transcript

Verdict is Benign. Variant got -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 id is 259539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-102625267-T-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
MMP20	NM_004771.4 linkuse as main transcript	c.53A>C	p.Lys18Thr	missense_variant	1/10	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3 linkuse as main transcript	c.53A>C	p.Lys18Thr	missense_variant	1/10	1	NM_004771.4	ENSP00000260228	P1
MMP20-AS1	ENST00000542119.1 linkuse as main transcript	n.87-1392T>G		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes

AF:

0.665

AC:

167017

AN:

251102

Hom.:

55914

AF XY:

0.667

AC XY:

90468

AN XY:

135716

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 SAS exome

AF:

0.699

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

Gnomad4 AFR exome

AF:

0.621

Gnomad4 AMR exome

AF:

0.674

Gnomad4 ASJ exome

AF:

0.608

Gnomad4 EAS exome

AF:

0.842

Gnomad4 SAS exome

AF:

0.695

Gnomad4 FIN exome

AF:

0.642

Gnomad4 NFE exome

AF:

0.648

Gnomad4 OTH exome

AF:

0.661

GnomAD4 genome

AF:

0.649

AC:

98662

AN:

151936

Hom.:

32181

Cov.:

AF XY:

0.653

AC XY:

48460

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.625

Gnomad4 AMR

AF:

0.673

Gnomad4 ASJ

AF:

0.594

Gnomad4 EAS

AF:

0.829

Gnomad4 SAS

AF:

0.711

Gnomad4 FIN

AF:

0.653

Gnomad4 NFE

AF:

0.642

Gnomad4 OTH

AF:

0.663

Alfa

AF:

0.649

Hom.:

72281

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Amelogenesis imperfecta hypomaturation type 2A2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

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

MutationTaster

Benign

0.86

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

Varity_R

0.060

gMVP

0.47

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