2-20003168-C-T

Variant names:

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.909G>A(p.Thr303Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,434 control chromosomes in the GnomAD database, including 38,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3189 hom., cov: 32)

Exomes 𝑓: 0.22 ( 34889 hom. )

Consequence

MATN3
NM_002381.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.74

Publications

12 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 2-20003168-C-T is Benign according to our data. Variant chr2-20003168-C-T is described in ClinVar as [Benign]. Clinvar id is 258649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATN3	NM_002381.5 link	c.909G>A	p.Thr303Thr	synonymous_variant	Exon 3 of 8	ENST00000407540.8	NP_002372.1	O15232-1
WDR35-DT	NR_110235.1 link	n.364-852C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATN3	ENST00000407540.8 link	c.909G>A	p.Thr303Thr	synonymous_variant	Exon 3 of 8	1	NM_002381.5	ENSP00000383894.3		O15232-1

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30046

AN:

151980

Hom.:

3184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.0326

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.197

GnomAD2 exomes

AF:

0.204

AC:

50833

AN:

249116

AF XY:

0.203

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.0284

Gnomad FIN exome

AF:

0.253

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.215

AC:

314342

AN:

1461334

Hom.:

34889

Cov.:

AF XY:

0.214

AC XY:

155473

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.156

AC:

5237

AN:

33474

American (AMR)

AF:

0.234

AC:

10483

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

5030

AN:

26130

East Asian (EAS)

AF:

0.0504

AC:

2002

AN:

39698

South Asian (SAS)

AF:

0.183

AC:

15750

AN:

86242

European-Finnish (FIN)

AF:

0.251

AC:

13397

AN:

53370

Middle Eastern (MID)

AF:

0.174

AC:

1000

AN:

5760

European-Non Finnish (NFE)

AF:

0.224

AC:

249171

AN:

1111600

Other (OTH)

AF:

0.203

AC:

12272

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

12177

24354

36532

48709

60886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.198

AC:

30083

AN:

152100

Hom.:

3189

Cov.:

AF XY:

0.198

AC XY:

14744

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.159

AC:

6611

AN:

41494

American (AMR)

AF:

0.216

AC:

3298

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

641

AN:

3466

East Asian (EAS)

AF:

0.0327

AC:

169

AN:

5172

South Asian (SAS)

AF:

0.180

AC:

870

AN:

4828

European-Finnish (FIN)

AF:

0.254

AC:

2684

AN:

10572

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.224

AC:

15246

AN:

67960

Other (OTH)

AF:

0.195

AC:

412

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1238

2475

3713

4950

6188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.210

Hom.:

5183

Bravo

AF:

0.193

Asia WGS

AF:

0.122

AC:

424

AN:

3478

EpiCase

AF:

0.214

EpiControl

AF:

0.213

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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:1

PreventionGenetics, part of Exact Sciences

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

-0.62

CADD

Benign

1.6

(source)

DANN

Benign

0.81

PhyloP100

-3.7

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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2-20003168-C-T

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