5-139307308-A-AT

Variant names:

• chr5-139307308-A-AT
• rs59150359
• NM_018834.6:c.-103dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_018834.6(MATR3):​c.-103dupT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 1,470,646 control chromosomes in the GnomAD database, including 332,573 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (25512 hom., cov: 0)
  • Exomes 𝑓: 0.67 (307061 hom.)
• Consequence: MATR3 NM_018834.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.822
• Publications: 2 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 -16 ACMG points.

• BP6: Variant 5-139307308-A-AT is Benign according to our data. Variant chr5-139307308-A-AT is described in ClinVar as Benign. ClinVar VariationId is 351117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

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.-103dupT		5_prime_UTR	Exon 2 of 15	NP_061322.2
	MATR3	NM_001400441.1		c.-103dupT		5_prime_UTR	Exon 3 of 16	NP_001387370.1	A8MXP9
	MATR3	NM_001400442.1		c.-103dupT		5_prime_UTR	Exon 5 of 18	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.-103dupT		5_prime_UTR	Exon 2 of 15	ENSP00000378284.3	P43243-1
	MATR3	ENST00000502929.5	TSL:2	c.-103dupT		5_prime_UTR	Exon 7 of 20	ENSP00000422319.1	A8MXP9
	MATR3	ENST00000618441.5	TSL:1	c.-103dupT		5_prime_UTR	Exon 2 of 15	ENSP00000482895.1	P43243-1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83158 AN: 151704 Hom.: 25500 Cov.: 0

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.576

GnomAD4 exome AF: 0.674 AC: 888567 AN: 1318824 Hom.: 307061 Cov.: 36 AF XY: 0.675 AC XY: 436745 AN XY: 647260

African (AFR) AF: 0.274 AC: 7824 AN: 28564

American (AMR) AF: 0.630 AC: 14201 AN: 22530

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 14482 AN: 20834

East Asian (EAS) AF: 0.252 AC: 8801 AN: 34988

South Asian (SAS) AF: 0.648 AC: 40726 AN: 62818

European-Finnish (FIN) AF: 0.629 AC: 24037 AN: 38242

Middle Eastern (MID) AF: 0.654 AC: 2495 AN: 3816

European-Non Finnish (NFE) AF: 0.705 AC: 741532 AN: 1052388

Other (OTH) AF: 0.631 AC: 34469 AN: 54644

GnomAD4 genome AF: 0.548 AC: 83208 AN: 151822 Hom.: 25512 Cov.: 0 AF XY: 0.542 AC XY: 40217 AN XY: 74168

African (AFR) AF: 0.286 AC: 11838 AN: 41420

American (AMR) AF: 0.589 AC: 8964 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2415 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1023 AN: 5160

South Asian (SAS) AF: 0.623 AC: 2997 AN: 4810

European-Finnish (FIN) AF: 0.620 AC: 6500 AN: 10478

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47545 AN: 67952

Other (OTH) AF: 0.576 AC: 1210 AN: 2102

Alfa AF: 0.630 Hom.: 3876

Bravo AF: 0.531

Asia WGS AF: 0.393 AC: 1367 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.82
Mutation Taster		=99/1	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: rs59150359; hg19: chr5-138642997;