NM_001393530.1:c.490C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001393530.1(MATN4):c.490C>A(p.Arg164Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,497,804 control chromosomes in the GnomAD database, including 72,291 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6881 hom., cov: 33)

Exomes 𝑓: 0.30 ( 65410 hom. )

Consequence

MATN4
NM_001393530.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.14

Publications

23 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.0037684E-6).

BP6

Variant 20-45304381-G-T is Benign according to our data. Variant chr20-45304381-G-T is described in ClinVar as Benign. ClinVar VariationId is 1338928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393530.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MATN4	NM_001393530.1	MANE Select	c.490C>A	p.Arg164Ser	missense	Exon 3 of 10	NP_001380459.1
MATN4	NM_003833.5		c.490C>A	p.Arg164Ser	missense	Exon 4 of 11	NP_003824.2
MATN4	NM_001393531.1		c.490C>A	p.Arg164Ser	missense	Exon 3 of 9	NP_001380460.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MATN4	ENST00000372756.6	TSL:1 MANE Select	c.490C>A	p.Arg164Ser	missense	Exon 3 of 10	ENSP00000361842.1
MATN4	ENST00000372754.5	TSL:5	c.490C>A	p.Arg164Ser	missense	Exon 2 of 10	ENSP00000361840.1
MATN4	ENST00000360607.10	TSL:1	c.490C>A	p.Arg164Ser	missense	Exon 3 of 9	ENSP00000353819.5

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42538

AN:

151970

Hom.:

6874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.743

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.286

GnomAD2 exomes

AF:

0.350

AC:

52282

AN:

149258

AF XY:

0.345

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.433

Gnomad ASJ exome

AF:

0.331

Gnomad EAS exome

AF:

0.767

Gnomad FIN exome

AF:

0.253

Gnomad NFE exome

AF:

0.282

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.299

AC:

401842

AN:

1345716

Hom.:

65410

Cov.:

AF XY:

0.301

AC XY:

197899

AN XY:

657590

show subpopulations

African (AFR)

AF:

0.189

AC:

5341

AN:

28228

American (AMR)

AF:

0.403

AC:

11057

AN:

27440

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

6735

AN:

19722

East Asian (EAS)

AF:

0.735

AC:

26962

AN:

36688

South Asian (SAS)

AF:

0.425

AC:

29316

AN:

69020

European-Finnish (FIN)

AF:

0.245

AC:

11767

AN:

48086

Middle Eastern (MID)

AF:

0.319

AC:

1647

AN:

5166

European-Non Finnish (NFE)

AF:

0.276

AC:

291650

AN:

1056086

Other (OTH)

AF:

0.314

AC:

17367

AN:

55280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

16633

33266

49900

66533

83166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10338

20676

31014

41352

51690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.280

AC:

42567

AN:

152088

Hom.:

6881

Cov.:

AF XY:

0.285

AC XY:

21180

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.198

AC:

8219

AN:

41518

American (AMR)

AF:

0.325

AC:

4972

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1151

AN:

3468

East Asian (EAS)

AF:

0.745

AC:

3826

AN:

5138

South Asian (SAS)

AF:

0.429

AC:

2068

AN:

4826

European-Finnish (FIN)

AF:

0.252

AC:

2666

AN:

10594

Middle Eastern (MID)

AF:

0.274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.276

AC:

18771

AN:

67932

Other (OTH)

AF:

0.288

AC:

608

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1542

3083

4625

6166

7708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.297

Hom.:

21028

Bravo

AF:

0.284

TwinsUK

AF:

0.276

AC:

1025

ALSPAC

AF:

0.263

AC:

1014

ESP6500AA

AF:

0.194

AC:

831

ESP6500EA

AF:

0.268

AC:

2226

ExAC

AF:

0.330

AC:

38194

Asia WGS

AF:

0.561

AC:

1948

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jan 27, 2022

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.011

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0000030

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.3

PhyloP100

2.1

PrimateAI

Uncertain

0.55

PROVEAN

Benign

1.6

REVEL

Benign

0.20

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.16

MPC

0.50

ClinPred

0.0079

GERP RS

3.8

Varity_R

0.24

gMVP

0.72

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over