rs80036770

Positions:

chr5-139319507-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018834.6(MATR3):c.1602+6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,599,072 control chromosomes in the GnomAD database, including 482 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 24 hom., cov: 32)

Exomes 𝑓: 0.023 ( 458 hom. )

Consequence

MATR3
NM_018834.6 splice_region, intron

Scores

Splicing: ADA: 0.00002836

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.742

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:

MATR3 (HGNC:):

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=-0.84).

BP6

Variant 5-139319507-A-G is Benign according to our data. Variant chr5-139319507-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 263208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-139319507-A-G is described in Lovd as [Benign]. Variant chr5-139319507-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0141 (2148/152094) while in subpopulation NFE AF= 0.0233 (1579/67902). AF 95% confidence interval is 0.0223. There are 24 homozygotes in gnomad4. There are 964 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2148 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATR3	NM_018834.6 linkuse as main transcript	c.1602+6A>G		splice_region_variant, intron_variant		ENST00000394805.8	NP_061322.2	P43243-1Q9H4N1A0A0R4J2E8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MATR3	ENST00000394805.8 linkuse as main transcript	c.1602+6A>G	splice_region_variant, intron_variant	1	NM_018834.6	ENSP00000378284.3	P43243-1
MATR3	ENST00000394800.6 linkuse as main transcript	c.1602+6A>G	splice_region_variant, intron_variant	5		ENSP00000378279.2	A8MXP9
MATR3	ENST00000502929.5 linkuse as main transcript	c.1602+6A>G	splice_region_variant, intron_variant	2		ENSP00000422319.1	A8MXP9

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2148

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00418

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.00637

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00934

Gnomad FIN

AF:

0.00943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0233

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.0141

AC:

3537

AN:

250350

Hom.:

AF XY:

0.0145

AC XY:

1970

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.00938

Gnomad ASJ exome

AF:

0.00628

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00908

Gnomad FIN exome

AF:

0.0121

Gnomad NFE exome

AF:

0.0215

Gnomad OTH exome

AF:

0.0173

GnomAD4 exome

AF:

0.0226

AC:

32642

AN:

1446978

Hom.:

458

Cov.:

AF XY:

0.0221

AC XY:

15892

AN XY:

720340

show subpopulations

Gnomad4 AFR exome

AF:

0.00373

Gnomad4 AMR exome

AF:

0.00978

Gnomad4 ASJ exome

AF:

0.00631

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.0264

Gnomad4 OTH exome

AF:

0.0215

GnomAD4 genome

AF:

0.0141

AC:

2148

AN:

152094

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

964

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00416

Gnomad4 AMR

AF:

0.0130

Gnomad4 ASJ

AF:

0.00637

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00956

Gnomad4 FIN

AF:

0.00943

Gnomad4 NFE

AF:

0.0233

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0163

Hom.:

Bravo

AF:

0.0143

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0207

EpiControl

AF:

0.0209

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 11, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Amyotrophic lateral sclerosis type 21

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 26, 2019	This variant is associated with the following publications: (PMID: 26493020) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.7

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.0

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