rs877826

Positions:

• chr5-139283108-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001400441.1(MATR3):​c.-178+6958T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,226 control chromosomes in the GnomAD database, including 23,161 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (23154 hom., cov: 33)
  • Exomes 𝑓: 0.66 (7 hom.)
• Consequence: MATR3 NM_001400441.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

Genes affected

MATR3 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATR3	NM_001400441.1	c.-178+6958T>G		intron_variant			NP_001387370.1
MATR3	NM_001400442.1	c.-178+3979T>G		intron_variant			NP_001387371.1
MATR3	NM_001400443.1	c.-178+6958T>G		intron_variant			NP_001387372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATR3	ENST00000394800.6	c.-301+3979T>G		intron_variant		5		ENSP00000378279.2
MATR3	ENST00000502929.5	c.-404+3979T>G		intron_variant		2		ENSP00000422319.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76085 AN: 152070 Hom.: 23160 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.658 AC: 25 AN: 38 Hom.: 7 Cov.: 0 AF XY: 0.615 AC XY: 16 AN XY: 26

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.719

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.500 AC: 76082 AN: 152188 Hom.: 23154 Cov.: 33 AF XY: 0.496 AC XY: 36892 AN XY: 74388

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.532

Alfa AF: 0.606 Hom.: 6643

Bravo AF: 0.478

Asia WGS AF: 0.380 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.50

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: rs877826; hg19: chr5-138618797;