5-139307308-A-AT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_018834.6(MATR3):c.-103dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 1,470,646 control chromosomes in the GnomAD database, including 332,573 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (25512 hom., cov: 0)
  • Exomes 𝑓: 0.67 (307061 hom.)
• Consequence: MATR3 NM_018834.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.822

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-139307308-A-AT is Benign according to our data. Variant chr5-139307308-A-AT is described in ClinVar as [Benign]. Clinvar id is 351117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATR3	NM_018834.6	c.-103dup		5_prime_UTR_variant	2/15	ENST00000394805.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATR3	ENST00000394805.8	c.-103dup		5_prime_UTR_variant	2/15	1	NM_018834.6	P1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83158 AN: 151704 Hom.: 25500 Cov.: 0

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.576

GnomAD4 exome AF: 0.674 AC: 888567 AN: 1318824 Hom.: 307061 Cov.: 36 AF XY: 0.675 AC XY: 436745 AN XY: 647260

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.695

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.648

Gnomad4 FIN exome AF: 0.629

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.548 AC: 83208 AN: 151822 Hom.: 25512 Cov.: 0 AF XY: 0.542 AC XY: 40217 AN XY: 74168

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.576

Alfa AF: 0.630 Hom.: 3876

Bravo AF: 0.531

Asia WGS AF: 0.393 AC: 1367 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Distal myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs59150359; hg19: chr5-138642997;