NM_018834.6:c.-43T>C

Variant names:

• chr5-139307373-T-C
• rs12153162
• NM_018834.6:c.-43T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018834.6(MATR3):​c.-43T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,508,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: MATR3 NM_018834.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 13 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High AC in GnomAdExome4 at 21 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.-43T>C		5_prime_UTR	Exon 2 of 15	NP_061322.2
	MATR3	NM_001400441.1		c.-43T>C		5_prime_UTR	Exon 3 of 16	NP_001387370.1	A8MXP9
	MATR3	NM_001400442.1		c.-43T>C		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.-43T>C		5_prime_UTR	Exon 2 of 15	ENSP00000378284.3	P43243-1
	MATR3	ENST00000502929.5	TSL:2	c.-43T>C		5_prime_UTR	Exon 7 of 20	ENSP00000422319.1	A8MXP9
	MATR3	ENST00000618441.5	TSL:1	c.-43T>C		5_prime_UTR	Exon 2 of 15	ENSP00000482895.1	P43243-1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 150970 Hom.: 0 Cov.: 30

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: 0.000192

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000369 AC: 7 AN: 189950 AF XY: 0.0000287

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: 0.000375

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000155 AC: 21 AN: 1357536 Hom.: 0 Cov.: 40 AF XY: 0.0000133 AC XY: 9 AN XY: 674228

African (AFR) AF: 0.00 AC: 0 AN: 26842

American (AMR) AF: 0.00 AC: 0 AN: 32372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23044

East Asian (EAS) AF: 0.00 AC: 0 AN: 33232

South Asian (SAS) AF: 0.00 AC: 0 AN: 72830

European-Finnish (FIN) AF: 0.000388 AC: 19 AN: 48944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5098

European-Non Finnish (NFE) AF: 9.44e-7 AC: 1 AN: 1059620

Other (OTH) AF: 0.0000180 AC: 1 AN: 55554

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 150970 Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1 AN XY: 73638

African (AFR) AF: 0.00 AC: 0 AN: 40974

American (AMR) AF: 0.00 AC: 0 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.000192 AC: 2 AN: 10392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67792

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.000138 Hom.: 1379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.031
DANN	Benign	0.63
PhyloP100		-1.6

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: rs12153162; hg19: chr5-138643062;