Variant 20-45293788-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001393530.1(MATN4):c.1725C>A(p.Asn575Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,610,250 control chromosomes in the GnomAD database, including 368 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 0.026 ( 174 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 194 hom. )

Consequence

MATN4
NM_001393530.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.314

Variant links:

Genes affected

MATN4 (HGNC:6910): (matrilin 4) This gene encodes a member of von Willebrand factor A domain-containing protein family. The proteins of this family are thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This family member is thought to be play a role in reorganizing and regenerating the corneal matrix in granular and lattice type I dystrophies. It may also be involved in wound healing in the dentin-pulp complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

MATN4 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=0.0015662313).

BP6

Variant 20-45293788-G-T is Benign according to our data. Variant chr20-45293788-G-T is described in ClinVar as [Benign]. Clinvar id is 785656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATN4	NM_001393530.1 linkuse as main transcript	c.1725C>A	p.Asn575Lys	missense_variant	10/10	ENST00000372756.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATN4	ENST00000372756.6 linkuse as main transcript	c.1725C>A	p.Asn575Lys	missense_variant	10/10	1	NM_001393530.1		O95460-2

Frequencies

GnomAD3 genomes

AF:

0.0263

AC:

4005

AN:

152226

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0911

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0205

GnomAD3 exomes

AF:

0.00688

AC:

1697

AN:

246672

Hom.:

AF XY:

0.00529

AC XY:

709

AN XY:

134114

show subpopulations

Gnomad AFR exome

AF:

0.0926

Gnomad AMR exome

AF:

0.00476

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000330

Gnomad OTH exome

AF:

0.00396

GnomAD4 exome

AF:

0.00275

AC:

4003

AN:

1457906

Hom.:

194

Cov.:

AF XY:

0.00237

AC XY:

1719

AN XY:

725448

show subpopulations

Gnomad4 AFR exome

AF:

0.0983

Gnomad4 AMR exome

AF:

0.00528

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000998

Gnomad4 OTH exome

AF:

0.00568

GnomAD4 genome

AF:

0.0263

AC:

4009

AN:

152344

Hom.:

174

Cov.:

AF XY:

0.0252

AC XY:

1879

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0909

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.00461

Hom.:

Bravo

AF:

0.0308

ESP6500AA

AF:

0.0858

AC:

378

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00826

AC:

1003

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 02, 2018

- -

MATN4-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.62

MetaRNN

Benign

0.0016

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.51

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.1

N;N;N;N;N

REVEL

Benign

0.046

Sift4G

Benign

0.27

T;T;T;T;T

Polyphen

0.0030

B;.;B;B;B

Vest4

0.14

MutPred

0.58

.;.;.;Gain of ubiquitination at N493 (P = 0.0069);.;

MVP

0.43

MPC

0.51

ClinPred

0.018

GERP RS

-3.2

Varity_R

0.38

gMVP

0.39

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