Variant 20-45297933-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001393530.1(MATN4):c.1564G>A(p.Gly522Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,613,578 control chromosomes in the GnomAD database, including 49,094 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.25 ( 5015 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44079 hom. )

Consequence

MATN4
NM_001393530.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.51

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016362667).

BP6

Variant 20-45297933-C-T is Benign according to our data. Variant chr20-45297933-C-T is described in ClinVar as [Benign]. Clinvar id is 3060323.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN4	NM_001393530.1 linkuse as main transcript	c.1564G>A	p.Gly522Ser	missense_variant	8/10	ENST00000372756.6	NP_001380459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN4	ENST00000372756.6 linkuse as main transcript	c.1564G>A	p.Gly522Ser	missense_variant	8/10	1	NM_001393530.1	ENSP00000361842		O95460-2

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38188

AN:

151984

Hom.:

5002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.251

GnomAD3 exomes

AF:

0.235

AC:

59064

AN:

251192

Hom.:

7527

AF XY:

0.227

AC XY:

30874

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.110

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.244

GnomAD4 exome

AF:

0.241

AC:

352481

AN:

1461476

Hom.:

44079

Cov.:

AF XY:

0.237

AC XY:

172496

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.255

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.251

AC:

38240

AN:

152102

Hom.:

5015

Cov.:

AF XY:

0.251

AC XY:

18693

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.255

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.293

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.241

Hom.:

11439

Bravo

AF:

0.256

TwinsUK

AF:

0.256

AC:

948

ALSPAC

AF:

0.255

AC:

984

ESP6500AA

AF:

0.254

AC:

1121

ESP6500EA

AF:

0.247

AC:

2126

ExAC

AF:

0.230

AC:

27918

Asia WGS

AF:

0.145

AC:

505

AN:

3478

EpiCase

AF:

0.238

EpiControl

AF:

0.235

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MATN4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

0.073

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0012

.;T;.;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.037

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.66

.;T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.85

.;L;.;.;.

MutationTaster

Benign

0.42

P;P;P;P;P;P;P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

0.47

N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.62

.;.;T;T;.

Sift4G

Benign

0.74

T;T;T;T;T

Polyphen

0.046

B;.;B;B;B

Vest4

0.19

MPC

0.50

ClinPred

0.0041

GERP RS

4.6

Varity_R

0.15

gMVP

0.52

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