5-139293986-A-G

Variant names:

• chr5-139293986-A-G
• rs772859892
• ENST00000618441.5:c.-220A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP6

The NM_001400445.1(MATR3):​c.-1189A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: MATR3 NM_001400445.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.48
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP6: Variant 5-139293986-A-G is Benign according to our data. Variant chr5-139293986-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3348614.Status of the report is no_assertion_criteria_provided, 0 stars.

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+181A>G		intron	N/A	NP_061322.2
	MATR3	NM_001400445.1		c.-1189A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_001387374.1	A8MXP9
	MATR3	NM_001194955.2		c.-220A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_001181884.1	A0A0R4J2E8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATR3	ENST00000618441.5	TSL:1	c.-220A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000482895.1	P43243-1
	MATR3	ENST00000618441.5	TSL:1	c.-220A>G		5_prime_UTR	Exon 1 of 15	ENSP00000482895.1	P43243-1
	MATR3	ENST00000394805.8	TSL:1 MANE Select	c.-178+181A>G		intron	N/A	ENSP00000378284.3	P43243-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 18728 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000169 AC: 19 AN: 1121304 Hom.: 1 Cov.: 30 AF XY: 0.0000261 AC XY: 14 AN XY: 536356

African (AFR) AF: 0.0000426 AC: 1 AN: 23500

American (AMR) AF: 0.000268 AC: 3 AN: 11206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16498

East Asian (EAS) AF: 0.00 AC: 0 AN: 26684

South Asian (SAS) AF: 0.00 AC: 0 AN: 33686

European-Finnish (FIN) AF: 0.000130 AC: 3 AN: 23124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3892

European-Non Finnish (NFE) AF: 0.00000960 AC: 9 AN: 937476

Other (OTH) AF: 0.0000663 AC: 3 AN: 45238

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MATR3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
PromoterAI		0.13	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs772859892; hg19: chr5-138629675;