chr20-45293997-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001393530.1(MATN4):c.1598G>A(p.Gly533Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,602,514 control chromosomes in the GnomAD database, including 46 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 (no stars).

Frequency

Genomes: 𝑓 0.0093 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 29 hom. )

Consequence

MATN4
NM_001393530.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.03

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=0.0044611692).

BP6

Variant 20-45293997-C-T is Benign according to our data. Variant chr20-45293997-C-T is described in ClinVar as [Benign]. Clinvar id is 3041719.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00931 (1418/152326) while in subpopulation AFR AF= 0.0324 (1349/41574). AF 95% confidence interval is 0.031. There are 17 homozygotes in gnomad4. There are 659 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN4	NM_001393530.1 link	c.1598G>A	p.Gly533Glu	missense_variant	Exon 9 of 10	ENST00000372756.6	NP_001380459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MATN4	ENST00000372756.6 link	c.1598G>A	p.Gly533Glu	missense_variant	Exon 9 of 10	1	NM_001393530.1	ENSP00000361842.1	O95460-2
MATN4	ENST00000372754.5 link	c.1721G>A	p.Gly574Glu	missense_variant	Exon 9 of 10	5		ENSP00000361840.1	O95460-1
MATN4	ENST00000360607.10 link	c.1475G>A	p.Gly492Glu	missense_variant	Exon 8 of 9	1		ENSP00000353819.5	O95460-4

Frequencies

GnomAD3 genomes

AF:

0.00930

AC:

1416

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00254

AC:

617

AN:

242574

Hom.:

AF XY:

0.00171

AC XY:

226

AN XY:

132072

show subpopulations

Gnomad AFR exome

AF:

0.0338

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.00101

AC:

1469

AN:

1450188

Hom.:

Cov.:

AF XY:

0.000882

AC XY:

637

AN XY:

722038

show subpopulations

Gnomad4 AFR exome

AF:

0.0345

Gnomad4 AMR exome

AF:

0.00189

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000720

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00931

AC:

1418

AN:

152326

Hom.:

Cov.:

AF XY:

0.00885

AC XY:

659

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0324

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.0109

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0327

AC:

144

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00310

AC:

376

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MATN4-related disorder

Benign:1

May 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

0.081

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

.;T;.;.;.

Eigen

Benign

0.098

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.83

.;T;T;T;T

MetaRNN

Benign

0.0045

T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.98

.;L;.;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.53

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.12

.;.;T;T;.

Sift4G

Benign

0.62

T;T;T;T;T

Polyphen

0.028

B;.;D;B;B

Vest4

0.14

MVP

0.87

MPC

1.3

ClinPred

0.015

GERP RS

3.4

Varity_R

0.17

gMVP

0.53

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