rs35973216

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_002381.5(MATN3):c.1406-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,599,264 control chromosomes in the GnomAD database, including 51,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4921 hom., cov: 33)

Exomes 𝑓: 0.25 ( 46295 hom. )

Consequence

MATN3
NM_002381.5 splice_region, intron

Scores

Splicing: ADA: 0.0001580

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.331

Publications

11 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 links:

WDR35-DT (HGNC:55818): (WDR35 divergent transcript)

WDR35-DT 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 (BayesDel_noAF=-0.77).

BP6

Variant 2-19993170-G-A is Benign according to our data. Variant chr2-19993170-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN3	NM_002381.5 link	c.1406-4C>T		splice_region_variant, intron_variant	Intron 7 of 7	ENST00000407540.8	NP_002372.1
WDR35-DT	NR_110235.1 link	n.291+2676G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATN3	ENST00000407540.8 link	c.1406-4C>T		splice_region_variant, intron_variant	Intron 7 of 7	1	NM_002381.5	ENSP00000383894.3

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38395

AN:

151846

Hom.:

4914

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.250

GnomAD2 exomes

AF:

0.251

AC:

61569

AN:

245432

AF XY:

0.247

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.252

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.250

AC:

362216

AN:

1447300

Hom.:

46295

Cov.:

AF XY:

0.249

AC XY:

179171

AN XY:

720676

show subpopulations

African (AFR)

AF:

0.255

AC:

8472

AN:

33166

American (AMR)

AF:

0.282

AC:

12550

AN:

44456

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

6861

AN:

26020

East Asian (EAS)

AF:

0.273

AC:

10791

AN:

39536

South Asian (SAS)

AF:

0.205

AC:

17599

AN:

85748

European-Finnish (FIN)

AF:

0.271

AC:

14380

AN:

53154

Middle Eastern (MID)

AF:

0.214

AC:

1222

AN:

5710

European-Non Finnish (NFE)

AF:

0.251

AC:

275649

AN:

1099678

Other (OTH)

AF:

0.246

AC:

14692

AN:

59832

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

12452

24904

37357

49809

62261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9290

18580

27870

37160

46450

<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:

0.253

AC:

38429

AN:

151964

Hom.:

4921

Cov.:

AF XY:

0.253

AC XY:

18800

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.255

AC:

10574

AN:

41460

American (AMR)

AF:

0.254

AC:

3875

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

878

AN:

3466

East Asian (EAS)

AF:

0.232

AC:

1202

AN:

5172

South Asian (SAS)

AF:

0.207

AC:

1000

AN:

4826

European-Finnish (FIN)

AF:

0.271

AC:

2852

AN:

10508

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.252

AC:

17134

AN:

67956

Other (OTH)

AF:

0.255

AC:

539

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1496

2992

4489

5985

7481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.253

Hom.:

2564

Bravo

AF:

0.253

Asia WGS

AF:

0.211

AC:

735

AN:

3476

EpiCase

AF:

0.242

EpiControl

AF:

0.242

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cranioectodermal dysplasia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Multiple Epiphyseal Dysplasia, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Multiple epiphyseal dysplasia type 5

Benign:1

Jan 12, 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.

Short rib-polydactyly syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.0

(source)

DANN

Benign

0.70

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

SpliceAI score (max)

0.010

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