5-139307139-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018834.6(MATR3):c.-177-90dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 780,898 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (1 hom.)
• Consequence: MATR3 NM_018834.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.379

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 -10 ACMG points.

• BP6: Variant 5-139307139-G-GT is Benign according to our data. Variant chr5-139307139-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 1212470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00843 (5341/633528) while in subpopulation AFR AF= 0.0186 (244/13098). AF 95% confidence interval is 0.0167. There are 1 homozygotes in gnomad4_exome. There are 2587 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 493 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATR3	NM_018834.6	c.-177-90dup		intron_variant		ENST00000394805.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATR3	ENST00000394805.8	c.-177-90dup		intron_variant		1	NM_018834.6	P1

Frequencies

GnomAD3 genomes AF: 0.00335 AC: 493 AN: 147266 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000790

Gnomad SAS AF: 0.00215

Gnomad FIN AF: 0.000208

Gnomad MID AF: 0.00974

Gnomad NFE AF: 0.000285

Gnomad OTH AF: 0.00297

GnomAD4 exome AF: 0.00843 AC: 5341 AN: 633528 Hom.: 1 AF XY: 0.00851 AC XY: 2587 AN XY: 303862

Gnomad4 AFR exome AF: 0.0186

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.00880

Gnomad4 EAS exome AF: 0.00915

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.00859

Gnomad4 NFE exome AF: 0.00805

Gnomad4 OTH exome AF: 0.00900

GnomAD4 genome AF: 0.00336 AC: 495 AN: 147370 Hom.: 1 Cov.: 32 AF XY: 0.00323 AC XY: 232 AN XY: 71774

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000791

Gnomad4 SAS AF: 0.00194

Gnomad4 FIN AF: 0.000208

Gnomad4 NFE AF: 0.000285

Gnomad4 OTH AF: 0.00294

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 25, 2020

- -

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: rs796858947; hg19: chr5-138642828;