chr5-139307044-ATAC-A

Variant names:

• chr5-139307044-ATAC-A
• rs144702367
• NM_018834.6:c.-177-190_-177-188delACT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018834.6(MATR3):​c.-177-190_-177-188delACT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 152,294 control chromosomes in the GnomAD database, including 86 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.028 (86 hom., cov: 32)
• Consequence: MATR3 NM_018834.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-139307044-ATAC-A is Benign according to our data. Variant chr5-139307044-ATAC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1212042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.028 (4262/152294) while in subpopulation NFE AF = 0.0473 (3218/68014). AF 95% confidence interval is 0.0459. There are 86 homozygotes in GnomAd4. There are 1908 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4262 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018834.6. 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.-177-190_-177-188delACT		intron	N/A	NP_061322.2
	MATR3	NM_001400441.1		c.-177-190_-177-188delACT		intron	N/A	NP_001387370.1	A8MXP9
	MATR3	NM_001400442.1		c.-177-190_-177-188delACT		intron	N/A	NP_001387371.1	A8MXP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATR3	ENST00000394805.8	TSL:1 MANE Select	c.-177-190_-177-188delACT		intron	N/A	ENSP00000378284.3	P43243-1
	MATR3	ENST00000502929.5	TSL:2	c.-177-190_-177-188delACT		intron	N/A	ENSP00000422319.1	A8MXP9
	MATR3	ENST00000618441.5	TSL:1	c.-177-190_-177-188delACT		intron	N/A	ENSP00000482895.1	P43243-1

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4264 AN: 152176 Hom.: 86 Cov.: 32

Gnomad AFR AF: 0.00862

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0280 AC: 4262 AN: 152294 Hom.: 86 Cov.: 32 AF XY: 0.0256 AC XY: 1908 AN XY: 74490

African (AFR) AF: 0.00859 AC: 357 AN: 41558

American (AMR) AF: 0.0143 AC: 219 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4830

European-Finnish (FIN) AF: 0.0280 AC: 297 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0473 AC: 3218 AN: 68014

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0324 Hom.: 17

Bravo AF: 0.0257

Asia WGS AF: 0.00840 AC: 29 AN: 3468

ClinVar

ClinVar submissions

Significance: Likely 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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

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: rs144702367; hg19: chr5-138642733;