Genetic Variant MATN3:c.791-1007G>A (chr2-20004293-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_002381.5(MATN3):c.791-1007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,156 control chromosomes in the GnomAD database, including 5,060 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5060 hom., cov: 32)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

MATN3
NM_002381.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002381.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN3	NM_002381.5	MANE Select	c.791-1007G>A		intron	N/A	NP_002372.1	O15232-1
	WDR35-DT	NR_110235.1		n.637C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MATN3	ENST00000407540.8	TSL:1 MANE Select	c.791-1007G>A	intron	N/A	ENSP00000383894.3	O15232-1
MATN3	ENST00000421259.2	TSL:1	c.790+1451G>A	intron	N/A	ENSP00000398753.2	O15232-2
MATN3	ENST00000856777.1		c.791-1007G>A	intron	N/A	ENSP00000526836.1

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36809

AN:

152016

Hom.:

5055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.617

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.197

Gnomad OTH

AF:

0.252

GnomAD4 exome

AF:

0.136

AC:

AN:

Hom.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.188

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.242

AC:

36830

AN:

152134

Hom.:

5060

Cov.:

AF XY:

0.247

AC XY:

18389

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.256

AC:

10638

AN:

41496

American (AMR)

AF:

0.269

AC:

4118

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

772

AN:

3468

East Asian (EAS)

AF:

0.616

AC:

3188

AN:

5174

South Asian (SAS)

AF:

0.391

AC:

1886

AN:

4822

European-Finnish (FIN)

AF:

0.176

AC:

1866

AN:

10580

Middle Eastern (MID)

AF:

0.318

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.197

AC:

13366

AN:

67992

Other (OTH)

AF:

0.260

AC:

549

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1399

2799

4198

5598

6997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.214

Hom.:

1943

Bravo

AF:

0.245

Asia WGS

AF:

0.491

AC:

1706

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over