5-139307373-T-A

Variant names:

Variant summary

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

The NM_018834.6(MATR3):c.-43T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,507,718 control chromosomes in the GnomAD database, including 369,403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27398 hom., cov: 30)

Exomes 𝑓: 0.71 ( 342005 hom. )

Consequence

MATR3
NM_018834.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.64

Publications

13 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-139307373-T-A is Benign according to our data. Variant chr5-139307373-T-A is described in ClinVar as Benign. ClinVar VariationId is 263207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATR3	NM_018834.6 link	c.-43T>A		5_prime_UTR_variant	Exon 2 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.-43T>A		5_prime_UTR_variant	Exon 2 of 15	1	NM_018834.6	ENSP00000378284.3		P43243-1
MATR3	ENST00000502929.5 link	c.-43T>A		5_prime_UTR_variant	Exon 7 of 20	2		ENSP00000422319.1		A8MXP9

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

85669

AN:

150886

Hom.:

27400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.705

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.647

Gnomad NFE

AF:

0.732

Gnomad OTH

AF:

0.597

GnomAD2 exomes

AF:

0.675

AC:

128217

AN:

189950

AF XY:

0.684

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.703

Gnomad ASJ exome

AF:

0.726

Gnomad EAS exome

AF:

0.314

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.738

Gnomad OTH exome

AF:

0.699

GnomAD4 exome

AF:

0.713

AC:

966915

AN:

1356720

Hom.:

342005

Cov.:

AF XY:

0.714

AC XY:

481010

AN XY:

673782

show subpopulations

African (AFR)

AF:

0.298

AC:

7996

AN:

26822

American (AMR)

AF:

0.682

AC:

22041

AN:

32332

Ashkenazi Jewish (ASJ)

AF:

0.717

AC:

16520

AN:

23034

East Asian (EAS)

AF:

0.331

AC:

11002

AN:

33214

South Asian (SAS)

AF:

0.694

AC:

50450

AN:

72700

European-Finnish (FIN)

AF:

0.679

AC:

33223

AN:

48900

Middle Eastern (MID)

AF:

0.689

AC:

3512

AN:

5098

European-Non Finnish (NFE)

AF:

0.741

AC:

784704

AN:

1059112

Other (OTH)

AF:

0.675

AC:

37467

AN:

55508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

13393

26786

40178

53571

66964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19408

38816

58224

77632

97040

<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:

0.567

AC:

85687

AN:

150998

Hom.:

27398

Cov.:

AF XY:

0.563

AC XY:

41482

AN XY:

73706

show subpopulations

African (AFR)

AF:

0.274

AC:

11243

AN:

41056

American (AMR)

AF:

0.609

AC:

9225

AN:

15140

Ashkenazi Jewish (ASJ)

AF:

0.705

AC:

2434

AN:

3454

East Asian (EAS)

AF:

0.247

AC:

1266

AN:

5124

South Asian (SAS)

AF:

0.656

AC:

3145

AN:

4792

European-Finnish (FIN)

AF:

0.660

AC:

6845

AN:

10378

Middle Eastern (MID)

AF:

0.647

AC:

189

AN:

292

European-Non Finnish (NFE)

AF:

0.732

AC:

49567

AN:

67760

Other (OTH)

AF:

0.596

AC:

1248

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1542

3085

4627

6170

7712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<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:

0.510

Hom.:

1379

Bravo

AF:

0.548

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not provided

Benign:1

Aug 10, 2019

GeneDx

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

-0.88

CADD

Benign

0.073

(source)

DANN

Benign

0.64

PhyloP100

-1.6

Mutation Taster

=119/181

disease causing (long InDel)

(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

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