rs28598872

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002381.5(MATN3):c.447C>T(p.Ala149Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,613,562 control chromosomes in the GnomAD database, including 163,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17151 hom., cov: 32)

Exomes 𝑓: 0.44 ( 146611 hom. )

Consequence

MATN3
NM_002381.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -5.19

Publications

18 publications found

Variant links:

Genes affected

MATN3 (HGNC:6909): (matrilin 3) This gene encodes a member of von Willebrand factor A domain containing protein family. This family of proteins is thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This protein contains two von Willebrand factor A domains; it is present in the cartilage extracellular matrix and has a role in the development and homeostasis of cartilage and bone. Mutations in this gene result in multiple epiphyseal dysplasia. [provided by RefSeq, Jul 2008]

MATN3 Gene-Disease associations (from GenCC):

multiple epiphyseal dysplasia type 5
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
spondyloepimetaphyseal dysplasia, matrilin-3 type
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

MATN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-20006087-G-A is Benign according to our data. Variant chr2-20006087-G-A is described in ClinVar as Benign. ClinVar VariationId is 195169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN3	NM_002381.5 link	c.447C>T	p.Ala149Ala	synonymous_variant	Exon 2 of 8	ENST00000407540.8	NP_002372.1	O15232-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATN3	ENST00000407540.8 link	c.447C>T	p.Ala149Ala	synonymous_variant	Exon 2 of 8	1	NM_002381.5	ENSP00000383894.3		O15232-1
MATN3	ENST00000421259.2 link	c.447C>T	p.Ala149Ala	synonymous_variant	Exon 2 of 7	1		ENSP00000398753.2		O15232-2

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71491

AN:

151854

Hom.:

17127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.521

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.495

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.477

GnomAD2 exomes

AF:

0.475

AC:

118253

AN:

249030

AF XY:

0.477

show subpopulations

Gnomad AFR exome

AF:

0.519

Gnomad AMR exome

AF:

0.493

Gnomad ASJ exome

AF:

0.414

Gnomad EAS exome

AF:

0.632

Gnomad FIN exome

AF:

0.438

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.443

AC:

647721

AN:

1461590

Hom.:

146611

Cov.:

AF XY:

0.447

AC XY:

324843

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.530

AC:

17754

AN:

33480

American (AMR)

AF:

0.487

AC:

21788

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

11016

AN:

26136

East Asian (EAS)

AF:

0.695

AC:

27580

AN:

39694

South Asian (SAS)

AF:

0.588

AC:

50756

AN:

86254

European-Finnish (FIN)

AF:

0.432

AC:

23072

AN:

53400

Middle Eastern (MID)

AF:

0.497

AC:

2865

AN:

5768

European-Non Finnish (NFE)

AF:

0.419

AC:

465693

AN:

1111784

Other (OTH)

AF:

0.451

AC:

27197

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

23164

46327

69491

92654

115818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14512

29024

43536

58048

72560

<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:

0.471

AC:

71565

AN:

151972

Hom.:

17151

Cov.:

AF XY:

0.476

AC XY:

35311

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.521

AC:

21585

AN:

41444

American (AMR)

AF:

0.496

AC:

7574

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1418

AN:

3468

East Asian (EAS)

AF:

0.637

AC:

3276

AN:

5146

South Asian (SAS)

AF:

0.587

AC:

2824

AN:

4812

European-Finnish (FIN)

AF:

0.433

AC:

4565

AN:

10552

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.422

AC:

28699

AN:

67960

Other (OTH)

AF:

0.483

AC:

1020

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1912

3825

5737

7650

9562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.437

Hom.:

9363

Bravo

AF:

0.472

Asia WGS

AF:

0.621

AC:

2158

AN:

3478

EpiCase

AF:

0.423

EpiControl

AF:

0.425

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 08, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Multiple epiphyseal dysplasia type 5

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.35

(source)

DANN

Benign

0.78

PhyloP100

-5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over