rs12153162

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
MATR3	NM_018834.6 linkuse as main transcript	c.-43T>A		5_prime_UTR_variant	2/15	ENST00000394805.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATR3	ENST00000394805.8 linkuse as main transcript	c.-43T>A		5_prime_UTR_variant	2/15	1	NM_018834.6	P1	P43243-1

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

GnomAD3 exomes

AF:

0.675

AC:

128217

AN:

189950

Hom.:

42259

AF XY:

0.684

AC XY:

71570

AN XY:

104664

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 SAS exome

AF:

0.698

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

Gnomad4 AFR exome

AF:

0.298

Gnomad4 AMR exome

AF:

0.682

Gnomad4 ASJ exome

AF:

0.717

Gnomad4 EAS exome

AF:

0.331

Gnomad4 SAS exome

AF:

0.694

Gnomad4 FIN exome

AF:

0.679

Gnomad4 NFE exome

AF:

0.741

Gnomad4 OTH exome

AF:

0.675

GnomAD4 genome

AF:

0.567

AC:

85687

AN:

150998

Hom.:

27398

Cov.:

AF XY:

0.563

AC XY:

41482

AN XY:

73706

show subpopulations

Gnomad4 AFR

AF:

0.274

Gnomad4 AMR

AF:

0.609

Gnomad4 ASJ

AF:

0.705

Gnomad4 EAS

AF:

0.247

Gnomad4 SAS

AF:

0.656

Gnomad4 FIN

AF:

0.660

Gnomad4 NFE

AF:

0.732

Gnomad4 OTH

AF:

0.596

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Amyotrophic lateral sclerosis type 21

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

0.073

Dann

Benign

0.64

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