Variant 2-20005919-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002381.5(MATN3):c.615G>A(p.Glu205=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,612,252 control chromosomes in the GnomAD database, including 163,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17086 hom., cov: 32)

Exomes 𝑓: 0.44 ( 146250 hom. )

Consequence

MATN3
NM_002381.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.310

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 2-20005919-C-T is Benign according to our data. Variant chr2-20005919-C-T is described in ClinVar as [Benign]. Clinvar id is 195170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATN3	NM_002381.5 linkuse as main transcript	c.615G>A	p.Glu205=	synonymous_variant	2/8	ENST00000407540.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATN3	ENST00000407540.8 linkuse as main transcript	c.615G>A	p.Glu205=	synonymous_variant	2/8	1	NM_002381.5	P1	O15232-1
MATN3	ENST00000421259.2 linkuse as main transcript	c.615G>A	p.Glu205=	synonymous_variant	2/7	1			O15232-2

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71353

AN:

151926

Hom.:

17062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.519

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:

0.430

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.476

GnomAD3 exomes

AF:

0.473

AC:

116386

AN:

245802

Hom.:

28198

AF XY:

0.475

AC XY:

63416

AN XY:

133418

show subpopulations

Gnomad AFR exome

AF:

0.515

Gnomad AMR exome

AF:

0.493

Gnomad ASJ exome

AF:

0.414

Gnomad EAS exome

AF:

0.631

Gnomad SAS exome

AF:

0.591

Gnomad FIN exome

AF:

0.435

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.467

GnomAD4 exome

AF:

0.443

AC:

646821

AN:

1460206

Hom.:

146250

Cov.:

AF XY:

0.447

AC XY:

324334

AN XY:

726294

show subpopulations

Gnomad4 AFR exome

AF:

0.528

Gnomad4 AMR exome

AF:

0.487

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.695

Gnomad4 SAS exome

AF:

0.588

Gnomad4 FIN exome

AF:

0.430

Gnomad4 NFE exome

AF:

0.419

Gnomad4 OTH exome

AF:

0.450

GnomAD4 genome

AF:

0.470

AC:

71427

AN:

152046

Hom.:

17086

Cov.:

AF XY:

0.474

AC XY:

35269

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.496

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.637

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.430

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.481

Alfa

AF:

0.429

Hom.:

17261

Bravo

AF:

0.471

Asia WGS

AF:

0.621

AC:

2158

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 08, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Multiple epiphyseal dysplasia type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.39

CADD

Benign

8.0

DANN

Benign

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over