5-139294274-T-G

Variant names:

• chr5-139294274-T-G
• rs3172746
• NM_018834.6:c.-178+469T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001400445.1(MATR3):​c.-901T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 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_001400445.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0190
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• distal myopathy with vocal cord weakness

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• amyotrophic lateral sclerosis type 21

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400445.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATR3	NM_018834.6	MANE Select	c.-178+469T>G		intron	N/A	NP_061322.2
	MATR3	NM_001400445.1		c.-901T>G		5_prime_UTR	Exon 1 of 15	NP_001387374.1	A8MXP9
	MATR3	NM_001400457.1		c.-520T>G		5_prime_UTR	Exon 1 of 15	NP_001387386.1	A0A0R4J2E8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATR3	ENST00000394805.8	TSL:1 MANE Select	c.-178+469T>G		intron	N/A	ENSP00000378284.3	P43243-1
	MATR3	ENST00000502929.5	TSL:2	c.-178+699T>G		intron	N/A	ENSP00000422319.1	A8MXP9
	MATR3	ENST00000618441.5	TSL:1	c.-178+246T>G		intron	N/A	ENSP00000482895.1	P43243-1

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

African (AFR) AF: 0.376 AC: 15579 AN: 41464

American (AMR) AF: 0.601 AC: 9188 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2182 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1101 AN: 5166

South Asian (SAS) AF: 0.641 AC: 3084 AN: 4814

European-Finnish (FIN) AF: 0.656 AC: 6932 AN: 10566

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48689 AN: 67952

Other (OTH) AF: 0.602 AC: 1262 AN: 2096

Alfa AF: 0.647 Hom.: 14437

Bravo AF: 0.569

Asia WGS AF: 0.425 AC: 1480 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.72
PhyloP100		0.019
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3172746; hg19: chr5-138629963;