rs17099008

Positions:

chr11-102611773-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.505A>C(p.Ile169Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00765 in 1,614,134 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0095 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0075 ( 237 hom. )

Consequence

MMP20
NM_004771.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.73

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=0.0022335649).

BP6

Variant 11-102611773-T-G is Benign according to our data. Variant chr11-102611773-T-G is described in ClinVar as [Benign]. Clinvar id is 301949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-102611773-T-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP20	NM_004771.4 linkuse as main transcript	c.505A>C	p.Ile169Leu	missense_variant	3/10	ENST00000260228.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP20	ENST00000260228.3 linkuse as main transcript	c.505A>C	p.Ile169Leu	missense_variant	3/10	1	NM_004771.4	P1
MMP20-AS1	ENST00000542119.1 linkuse as main transcript	n.86+4321T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00949

AC:

1444

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.00464

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0817

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.0128

AC:

3218

AN:

251360

Hom.:

101

AF XY:

0.0135

AC XY:

1831

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0922

Gnomad SAS exome

AF:

0.0275

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00325

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.00747

AC:

10913

AN:

1461812

Hom.:

237

Cov.:

AF XY:

0.00808

AC XY:

5878

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0120

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0832

Gnomad4 SAS exome

AF:

0.0288

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00364

Gnomad4 OTH exome

AF:

0.00825

GnomAD4 genome

AF:

0.00947

AC:

1442

AN:

152322

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

748

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0124

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0821

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00350

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00762

Hom.:

Bravo

AF:

0.0104

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.0132

AC:

1602

Asia WGS

AF:

0.0350

AC:

121

AN:

3478

EpiCase

AF:

0.00480

EpiControl

AF:

0.00261

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Amelogenesis imperfecta hypomaturation type 2A2

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.9

REVEL

Benign

0.10

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.051

Polyphen

0.0030

Vest4

0.14

MutPred

0.74

Gain of sheet (P = 0.1451);

MPC

0.096

ClinPred

0.038

GERP RS

1.8

Varity_R

0.62

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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