rs14109

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The ENST00000505625.5(MATR3):n.6972T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 454,522 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.033 ( 115 hom., cov: 33)

Exomes 𝑓: 0.034 ( 237 hom. )

Consequence

MATR3
ENST00000505625.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.24

Publications

7 publications found

Variant links:

Genes affected

MATR3 (HGNC:6912): (matrin 3) This gene encodes a nuclear matrix protein, which is proposed to stabilize certain messenger RNA species. Mutations of this gene are associated with distal myopathy 2, which often includes vocal cord and pharyngeal weakness. Alternatively spliced transcript variants, including read-through transcripts composed of the upstream small nucleolar RNA host gene 4 (non-protein coding) and matrin 3 gene sequence, have been identified. Pseudogenes of this gene are located on chromosomes 1 and X. [provided by RefSeq, Aug 2013]

MATR3 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis type 21
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
distal myopathy with vocal cord weakness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MATR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 5-139330103-T-C is Benign according to our data. Variant chr5-139330103-T-C is described in ClinVar as Benign. ClinVar VariationId is 351159.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0333 (5070/152310) while in subpopulation NFE AF = 0.0479 (3258/68018). AF 95% confidence interval is 0.0465. There are 115 homozygotes in GnomAd4. There are 2533 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 5070 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATR3	NM_018834.6 link	c.*708T>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000394805.8	NP_061322.2	P43243-1Q9H4N1A0A0R4J2E8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATR3	ENST00000394805.8 link	c.*708T>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_018834.6	ENSP00000378284.3		P43243-1
MATR3	ENST00000502929.5 link	c.*708T>C		3_prime_UTR_variant	Exon 20 of 20	2		ENSP00000422319.1		A8MXP9

Frequencies

GnomAD3 genomes

AF:

0.0333

AC:

5074

AN:

152192

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00811

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0420

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00806

Gnomad FIN

AF:

0.0632

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0479

Gnomad OTH

AF:

0.0339

GnomAD2 exomes

AF:

0.0319

AC:

4355

AN:

136562

AF XY:

0.0313

show subpopulations

Gnomad AFR exome

AF:

0.00730

Gnomad AMR exome

AF:

0.0315

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.000190

Gnomad FIN exome

AF:

0.0624

Gnomad NFE exome

AF:

0.0502

Gnomad OTH exome

AF:

0.0384

GnomAD4 exome

AF:

0.0344

AC:

10385

AN:

302212

Hom.:

237

Cov.:

AF XY:

0.0321

AC XY:

5522

AN XY:

172244

show subpopulations

African (AFR)

AF:

0.00865

AC:

AN:

8554

American (AMR)

AF:

0.0313

AC:

855

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

118

AN:

10786

East Asian (EAS)

AF:

0.000217

AC:

AN:

9210

South Asian (SAS)

AF:

0.00979

AC:

584

AN:

59650

European-Finnish (FIN)

AF:

0.0538

AC:

688

AN:

12790

Middle Eastern (MID)

AF:

0.0330

AC:

AN:

1150

European-Non Finnish (NFE)

AF:

0.0472

AC:

7492

AN:

158752

Other (OTH)

AF:

0.0380

AC:

534

AN:

14046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

658

1316

1975

2633

3291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.0333

AC:

5070

AN:

152310

Hom.:

115

Cov.:

AF XY:

0.0340

AC XY:

2533

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00808

AC:

336

AN:

41574

American (AMR)

AF:

0.0418

AC:

640

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00786

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0632

AC:

671

AN:

10610

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0479

AC:

3258

AN:

68018

Other (OTH)

AF:

0.0336

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

252

504

756

1008

1260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0352

Hom.:

Bravo

AF:

0.0324

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis type 21

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

-0.31

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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