5-139294274-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018834.6(MATR3):c.-178+469T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,020 control chromosomes in the GnomAD database, including 27,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.58 (27933 hom., cov: 31)
• Consequence: MATR3 NM_018834.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0190

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-139294274-T-G is Benign according to our data. Variant chr5-139294274-T-G is described in ClinVar as [Benign]. Clinvar id is 1282403.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATR3	NM_018834.6	c.-178+469T>G		intron_variant		ENST00000394805.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATR3	ENST00000394805.8	c.-178+469T>G		intron_variant		1	NM_018834.6	P1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88687 AN: 151902 Hom.: 27916 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.584 AC: 88746 AN: 152020 Hom.: 27933 Cov.: 31 AF XY: 0.578 AC XY: 42915 AN XY: 74290

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.602

Alfa AF: 0.672 Hom.: 9229

Bravo AF: 0.569

Asia WGS AF: 0.425 AC: 1480 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.6
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3172746; hg19: chr5-138629963;